International Journal of Inflammation The latest articles from Hindawi © 2017 , Hindawi Limited . All rights reserved. Neutrophil Extracellular Trap Production in Patients with Colorectal Cancer In Vitro Sun, 30 Jul 2017 08:19:54 +0000 Purpose. Neutrophil Extracellular Traps (NETs) are extracellular neutrophil derived DNA webs which have been implicated in cancer progression and in the development of metastases. NETs production in patients with colorectal cancer was investigated to elucidate their role and prognostic significance. Methods. Systemic neutrophils were isolated from consecutive patients with colorectal cancer and from age-matched healthy volunteers. Neutrophils were stimulated to produce NETs which were quantified by a measure of the fluorescence of the extracellular DNA. The impact of cancer location, tumour stage, and patient outcomes (complications, length of stay, and mortality) on NET production was investigated. Results. Quantification of NET formation was performed in patients with colorectal cancer () and in well-matched healthy individuals (). Significant increases in NETs production in response to no stimulant (9,735 AFU versus 11347 AFU, ), IL-8 (8,644 AFU versus 11,915 AFU, ), and LPS (10,576 AFU versus 12,473 AFU, ) were identified in patients with colorectal cancer. A significant increase in NETs production in response to fMLP was detected in patients who developed significant postoperative complications (11,760 AFU versus 18,340 AFU, ) and who had a prolonged hospital recovery (9,008 AFU versus 12,530 AFU, ). An increase in NETs production was also observed in patients who died, but this did not reach statistical significance. Cancer location and tumour stage did not appear to affect preoperative NETs production. Conclusions. Patients with colorectal cancer have significantly increased NETs production in vitro when compared to healthy volunteers, possibly implicating them in cancer development. Adverse patient outcomes were associated with increased preoperative NETs production, which highlights them as potential therapeutic targets. J. J. R. Richardson, C. Hendrickse, F. Gao-Smith, and D. R. Thickett Copyright © 2017 J. J. R. Richardson et al. All rights reserved. From Inflammation to Current and Alternative Therapies Involved in Wound Healing Tue, 25 Jul 2017 00:00:00 +0000 Wound healing is a complex event that develops in three overlapping phases: inflammatory, proliferative, and remodeling. These phases are distinct in function and histological characteristics. However, they depend on the interaction of cytokines, growth factors, chemokines, and chemical mediators from cells to perform regulatory events. In this article, we will review the pathway in the skin healing cascade, relating the major chemical inflammatory mediators, cellular and molecular, as well as demonstrating the local and systemic factors that interfere in healing and disorders associated with tissue repair deficiency. Finally, we will discuss the current therapeutic interventions in the wounds treatment, and the alternative therapies used as promising results in the development of new products with healing potential. Mariana Barreto Serra, Wermerson Assunção Barroso, Neemias Neves da Silva, Selma do Nascimento Silva, Antonio Carlos Romão Borges, Iracelle Carvalho Abreu, and Marilene Oliveira da Rocha Borges Copyright © 2017 Mariana Barreto Serra et al. All rights reserved. Is Neutrophil-to-Lymphocyte Ratio a Predictor of Coronary Artery Disease in Western Indians? Mon, 24 Jul 2017 06:58:17 +0000 Introduction. The current study was designed to evaluate the association of neutrophil-to-lymphocyte ratio (NLR) with coronary artery disease (CAD) presence. We also aimed to propose a suitable cut-off of NLR for diagnosis of CAD in Western Indians. Methods. Total 324 patients undergoing coronary angiography were enrolled and were subdivided into two groups: group 1 (; population without CAD) and group 2 (; population with CAD). Results. The results indicated significant () positive association between elevated levels of WBC, neutrophil, monocyte, NLR, hs-CRP, CPK-MB, and troponin I and disease presence. According to subgroup analysis, the association was more profound in male and older population. Among all the markers NLR showed the strongest predictive potential for CAD with highest odds ratio (1.495; 95% CI: 0.942–2.371; ). Optimum cut-off of NLR for diagnosis of CAD was 2.13 (AUC-0.823; ; sensitivity: 83.64%; specificity: 63.46%). Association of NLR with other biochemical markers such as hs-CRP, CPK-MB, and troponin I was also observed in quartile analysis. Conclusion. NLR is a simple indicator that could be effectively used for the diagnosis of CAD with a cut-off of 2.13 in Western Indian population. Kamal Sharma, Alap K. Patel, Komal H. Shah, and Ashwati Konat Copyright © 2017 Kamal Sharma et al. All rights reserved. Impaired mRNA Expression of the Migration Related Chemokine Receptor CXCR4 in Mesenchymal Stem Cells of COPD Patients Wed, 19 Jul 2017 07:48:25 +0000 Defective tissue repair and remodeling are main aspects of Chronic Obstructive Pulmonary Disease (COPD) pathophysiology. Bone marrow mesenchymal stem cells (BM-MSCs) have been implicated in this direction, as their functional impairment and recruitment could possibly contribute to disease development and progression. The present study characterizes for the first time the expression of migration related chemokine receptors and their ligands in BM-MSCs from COPD patients. CXCR4/SDF1a and CCR7/CCL19-CCL21 mRNA levels were evaluated in BM-MSCs obtained from twelve COPD patients and seven healthy donors. SDF1a protein levels in sera and BM-MSCs’ conditioned media were also evaluated. CXCR4, SDF1a, CCL19, and CCL21 mRNA levels were significantly reduced in COPD BM-MSCs while CCR7 levels were undetectable. Notably, SDF1a protein levels were marginally elevated in both patient sera and BM-MSCs’ conditioned media while the increase in SDF1a serum levels significantly correlated with disease severity in COPD. Our findings show posttranscriptional regulation of SDF1a levels in BM-MSCs of COPD patients and significant downregulation of SDF1a and CXCR4 mRNA indicating an involvement of the SDF1a signaling pathway in the disease pathophysiology. K. Karagiannis, A. Proklou, E. Tsitoura, I. Lasithiotaki, C. Kalpadaki, D. Moraitaki, I. Sperelakis, G. Kontakis, K. M. Antoniou, and N. Tzanakis Copyright © 2017 K. Karagiannis et al. All rights reserved. An In Vitro Model of Gastric Inflammation and Treatment with Cobalamin Tue, 06 Jun 2017 00:00:00 +0000 Pernicious anaemia (PA) is an autoimmune condition where antibodies target intrinsic factor and parietal cells, reducing the patient’s ability to absorb cobalamin promoting atrophic gastritis. Treatment guidelines are based on excretion data of hydroxocobalamin from healthy individuals obtained 50 years ago. This manuscript describes the use of phorbol 12-myristate 13-acetate (PMA) to stimulate low grade inflammation in an epithelial colorectal cell line to assess the efficacy of methylcobalamin and hydroxocobalamin. Nitric oxide increased significantly in cells exposed to higher doses of PMA (100 ng/ml, 150 ng/ml, and 200 ng/ml) accompanied by a loss of the characteristic cobblestone morphology with no negative effect on cell activity or viability. A significant reduction in nitric oxide production was associated with the addition of 200 pg/ml hydroxocobalamin, alongside a return to the characteristic cobblestone morphology. This study highlights the use of PMA to promote low grade inflammation in human cell lines to model gastric inflammation associated with autoimmunity; furthermore it raises questions regarding the concentration of cobalamin administered clinically to restore cell functionality, feasibly allowing the patient to receive reduced quantity of the vitamin more regularly, providing the patient with levels which are akin to dietary intake. T. R. Elliott and A. L. Guildford Copyright © 2017 T. R. Elliott and A. L. Guildford. All rights reserved. Does Inhalation of Virgin Coconut Oil Accelerate Reversal of Airway Remodelling in an Allergic Model of Asthma? Sun, 04 Jun 2017 08:15:55 +0000 Many studies have been done to evaluate the effect of various natural products in controlling asthma symptoms. Virgin coconut oil (VCO) is known to contain active compounds that have beneficial effects on human health and diseases. The objective of this study was to evaluate the effect of VCO inhalation on airway remodelling in a rabbit model of allergic asthma. The effects of VCO inhalation on infiltration of airway inflammatory cells, airway structures, goblet cell hyperplasia, and cell proliferation following ovalbumin induction were evaluated. Allergic asthma was induced by a combination of ovalbumin and alum injection and/or followed by ovalbumin inhalation. The effect of VCO inhalation was then evaluated via the rescue or the preventive route. Percentage of inflammatory cells infiltration, thickness of epithelium and mucosa regions, and the numbers of goblet and proliferative cells were reduced in the rescue group but not in preventive group. Analysis using a gas chromatography-mass spectrometry found that lauric acid and capric acid were among the most abundant fatty acids present in the sample. Significant improvement was observed in rescue route in alleviating the asthma symptoms, which indicates the VCO was able to relieve asthma-related symptoms more than preventing the onset of asthma. N. A. Kamalaldin, S. A. Sulaiman, M. R. Yusop, and B. Yahaya Copyright © 2017 N. A. Kamalaldin et al. All rights reserved. High Vitamin D Levels May Downregulate Inflammation in Patients with Behçet’s Disease Sun, 04 Jun 2017 07:02:36 +0000 Vitamin D plays a significant role in the immune system modulation and may confer a protective role in autoimmune diseases. We conducted a case-control study to compare 25(OH)D levels in patients with BD who were managed at a regional rheumatology programme in the midwest region of Ireland compared to matched controls. Healthy controls were selected from the Irish health system and matched in 1 : 5 ratio for age, sex, and the month of the year. 25(OH)D levels <20 nmol/L were classified as deficient while levels between 20 and 40 nmol/L were classified as insufficient. Differences between groups were assessed using Mann–Whitney test and associations between cases and controls were expressed as odds ratios and 95% confidence intervals. Nineteen patients with BD were compared with 95 controls matched by age, sex, and month of blood draw. 25(OH)D levels were significantly higher in patients in BD than in matched controls (median values: 45 nmol/L versus 22 nmol/L, ) and tended to be lower in patients with active disease than in those without (median values: 35 nmol/L (IQR: 22.75–47.25 nm/L) versus 50 nmol/L (IQR: 35–67 nmol/L), ). Compared to controls, patients with BD were significantly less likely to have 25(OH)D deficiency or insufficiency (OR: 0.09, 95% CI: 0.03–0.28, ). Our findings suggest a possible role for 25(OH)D in modifying the inflammatory response in BD and uncover a potential opportunity to assess whether correction of Vit D deficiency confers protective benefits. Fahd Adeeb, Maria Usman Khan, Xia Li, Austin G. Stack, Joseph Devlin, and Alexander D. Fraser Copyright © 2017 Fahd Adeeb et al. All rights reserved. Alleviating Promotion of Inflammation and Cancer Induced by Nonsteroidal Anti-Inflammatory Drugs Wed, 10 May 2017 06:31:39 +0000 Clinical Relevance. Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) including aspirin are of intensive use nowadays. These drugs exert their activity via the metabolism of arachidonic acid (AA) by cyclooxygenase inhibition. Though beneficial for health in some instances, both unspecific and specific cyclooxygenase inhibitor activity interfere with AA metabolism producing also proinflammatory lipids that may promote cancer. Materials and Methods. This review is based on available literature on clinical uses, biochemical investigations, molecular medicine, pharmacology, toxicity, and epidemiology-clinical studies on NSAIDs and other drugs that may be used accordingly, which was collected from electronic (SciFinder, Medline, Science Direct, and ACS among others) and library searches of books and journals. Results. Relevant literature supports the notion that NDSAID use may also promote proinflammatory biochemical events that are also related to precancerous predisposition. Several agents are proposed that may be employed in immediate future to supplement and optimize treatment with NSAIDs. In this way serious side effects arising from promotion of inflammation and cancer, especially in chronic NSAID users and high risk groups of patients, could be avoided. Anthony M. Kyriakopoulos, Markus Nagl, Stella Baliou, and Vasilleios Zoumpourlis Copyright © 2017 Anthony M. Kyriakopoulos et al. All rights reserved. The Role of Toll-Like Receptors in Autoimmune Diseases through Failure of the Self-Recognition Mechanism Wed, 03 May 2017 08:39:44 +0000 Toll-like receptors (TLRs), part of the innate immune system that recognises molecular signatures, are important in the recognition of pathogenic components. However, when specific cellular contexts develop in which TLRs are inappropriately activated by self-components, this may lead to sterile inflammation and result in the occurrence of autoimmunity. This review analyses the available data regarding TLR biochemistry, the specific mechanisms which are brought about by TLR activation, and the importance of these mechanisms in the light of any existing and potential therapies in the field of autoimmunity. Mark Farrugia and Byron Baron Copyright © 2017 Mark Farrugia and Byron Baron. All rights reserved. Mycobacterium avium Subsp. paratuberculosis Induces Specific IgE Production in Japanese People with Allergies Mon, 24 Apr 2017 00:00:00 +0000 Background. The prevalence of allergies is steadily increasing worldwide; however, the pathogenesis is still unclear. We hypothesized that Mycobacterium avium subsp. paratuberculosis (MAP) may contribute to allergy development. This organism can be present in dairy foods, it can elicit an immunomodulatory switch from a Th1 to a Th2 response, and it has been speculated that it is linked to several human autoimmune diseases. To determine the contribution, sera from 99 individuals with various atopic disorders and 45 healthy nonallergic controls were assessed for total IgE levels and successively for MAP-specific IgE by ELISA. Results. The mean total serum IgE level in allergic patients was  IU/mL, and in the healthy controls it was  IU/mL (AUC = 0.88; ). Among the patient groups, 50 of the 99 subjects had increased IgE total level ≥ 150 IU/mL, while 49 subjects had IgE ≤ 150 IU/mL (mean level:  IU/mL versus  IU/mL; ). Additionally, 6 out of 50 subjects (12%) with IgE ≥ 150 IU/mL and none (0%) with IgE ≤ 150 IU/mL were positive for specific MAP IgE (AUC = 0.63; ). Conclusion. The present study revealed that MAP has the ability to induce specific IgE and might contribute to the induction of allergic inflammation in genetically predisposed individuals. D. Cossu, S. Otsubo, Y. Otsubo, S. Eda, T. Suzuki, Y. Iwao, T. Kuribayashi, S. Yamamoto, L. A. Sechi, and E. Momotani Copyright © 2017 D. Cossu et al. All rights reserved. Identification of a Novel Alternatively Spliced Form of Inflammatory Regulator SWAP-70-Like Adapter of T Cells Mon, 24 Apr 2017 00:00:00 +0000 Activation of naive CD4+ T cells results in the development of several distinct subsets of effector Th cells, including Th2 cells that play a pivotal role in allergic inflammation and helminthic infections. SWAP-70-like adapter of T cells (SLAT), also known as Def6 or IBP, is a guanine nucleotide exchange factor for small GTPases, which regulates CD4+ T cell inflammatory responses by controlling Ca2+/NFAT signaling. In this study, we have identified a novel alternatively spliced isoform of SLAT, named SLAT2, which lacks the region encoded by exons 2–7 of the Def6 gene. SLAT2 was selectively expressed in differentiated Th2 cells after the second round of in vitro stimulation, but not in differentiated Th1, Th17, or regulatory T (Treg) cells. Functional assays revealed that SLAT2 shared with SLAT the ability to enhance T cell receptor- (TCR-) mediated activation of NFAT and production of IL-4 but was unable to enhance TCR-induced adhesion to ICAM-1. Ectopic expression of SLAT2 or SLAT in Jurkat T cells resulted in the expression of distinct forms of filopodia, namely, short versus long ones, respectively. These results demonstrate that modulating either SLAT2 or SLAT protein expression could play critical roles in cytokine production and actin reorganization during inflammatory immune responses. Marie Hashimoto, Jun-ichi Nagao, Shojiro Ikezaki, Sonoko Tasaki, Ken-ichi Arita-Morioka, Yuka Narita, Tamaki Cho, Kenji Yuasa, Amnon Altman, and Yoshihiko Tanaka Copyright © 2017 Marie Hashimoto et al. All rights reserved. The Level of Oxidative Neutrophil Response When Determining Endotoxin Activity Assay: A New Biomarker for Defining the Indications and Effectiveness of Intensive Care in Patients with Sepsis Wed, 12 Apr 2017 09:56:55 +0000 Background. To analyse the clinical informativity of the neutrophil oxidative response level (“Response”) during an Endotoxin Activity Assay (EAA) as a new biomarker defining the indications and effectiveness of intensive care in cardiac surgical patients with septic complications. Methods. Blood samples were taken from 198 adult patients who were admitted to the ICU after cardiac surgery (SIRS: 34, MODS: 36, and sepsis: 128). The composite of laboratory studies included CRP, PCT, EAA with “Response” level, and presepsin. Results. 83% of patients had a “normal” neutrophil response, 12% of patients had a low neutrophil response, and 5% of patients had a critically low neutrophil response. Patients with critically low responses had the lowest values of the EAA and the highest concentrations of PSP and D-dimer (). Conclusions. EAA results should be interpreted with the level of neutrophil response. “Response” > 0.5 has a negative predictive value; the EAA < 0.6 at “Response” < 0.5 may indicate a high level of endotoxaemia. Michael Yaroustovsky, Ekaterina Rogalskaya, Marina Plyushch, Ludmila Klimovich, Nataliya Samsonova, and Marina Abramyan Copyright © 2017 Michael Yaroustovsky et al. All rights reserved. Curcumin Inhibits NTHi-Induced MUC5AC Mucin Overproduction in Otitis Media via Upregulation of MAPK Phosphatase MKP-1 Wed, 12 Apr 2017 07:35:01 +0000 Otitis media (OM), characterized by the presence of mucus overproduction and excess inflammation in the middle ear, is the most common childhood infection. Nontypeable Haemophilus influenzae (NTHi) pathogen is responsible for approximately one-third of episodes of bacteria-caused OM. Current treatments for bacterial OM rely on the systemic use of antibiotics, which often leads to the emergence of multidrug resistant bacterial strains. Therefore there is an urgent need for developing alternative therapies strategies for controlling mucus overproduction in OM. MUC5AC mucin has been shown to play a critical role in the pathogenesis of OM. Here we show that curcumin derived from Curcuma longa plant is a potent inhibitor of NTHi-induced MUC5AC mucin expression in middle ear epithelial cells. Curcumin inhibited MUC5AC expression by suppressing activation of p38 MAPK by upregulating MAPK phosphatase MKP-1. Thus, our study identified curcumin as a potential therapeutic for inhibiting mucin overproduction in OM by upregulating MKP-1, a known negative regulator of inflammation. Anuhya Sharma Konduru, Shingo Matsuyama, Byung-Cheol Lee, Kensei Komatsu, and Jian-Dong Li Copyright © 2017 Anuhya Sharma Konduru et al. All rights reserved. High-Sensitive C-Reactive Protein Levels in a Group of Syrian University Male Students and Its Associations with Smoking, Physical Activity, Anthropometric Measurements, and Some Hematologic Inflammation Biomarkers Mon, 10 Apr 2017 07:39:38 +0000 In Syria, health risk data on young males are limited. Hence, the aim of the present study was to evaluate cardiovascular disease (CVD) risk factors along with C-reactive protein levels measured by high-sensitive method (hsCRP) in a group of healthy males of university students (, 18–25 years old). Participants’ anthropometric characteristics; alcohol drinking, smoking, and physical activity habits; parents medical history; and some inflammatory biomarkers were inspected for their associations with hsCRP. Results. Regarding hsCRP level, 19 participants were at average (1–3 mg/L) and 13 were at high (>3 mg/L) risk of CVD. Nonparametric statistical tests ( value < 0.05) revealed that hsCRP level was higher in participants who had high body mass index (BMI), had high BMI with high waist-to-hip ratio (WHR), or did not practice sport frequently. Unexpectedly, it did not vary between smokers and nonsmokers. In general, it correlated positively with anthropometric and erythrocyte sedimentation rate (ESR) measurements. Nevertheless, it negatively correlated with sports practicing in overall and nonsmoker groups and in participants whose parents were without medical history. Finally, when participants with high BMI were smokers, did not practice sport frequently, or had a parent with medical history, their hsCRP levels were higher than others who had the same circumstances but with low BMI. Wafika Zarzour, Nada Dehneh, and Mazen Rajab Copyright © 2017 Wafika Zarzour et al. All rights reserved. Transcriptional and Molecular Pathways Activated in Mesenteric Adipose Tissue and Intestinal Mucosa of Crohn’s Disease Patients Sun, 09 Apr 2017 00:00:00 +0000 Crohn’s disease (CD) is a chronic inflammatory disorder, characterized by cytokine imbalance and transcription signaling pathways activation. In addition, the increase of mesenteric adipose tissue (MAT) near the affected intestinal area is a hallmark of CD. Therefore, we evaluated the transcription signaling pathways and cytokines expression in intestinal mucosa and MAT of active CD patients. Ten patients with ileocecal CD and eight with noninflammatory diseases were studied. The biopsies of intestinal mucosa and MAT were snap-frozen and protein expression was determined by immunoblotting. RNA levels were measured by qPCR. The pIkB/IkB ratio and TNFα level were significantly higher in intestinal mucosa of CD when compared to controls. However, STAT1 expression was similar between intestinal mucosa of CD and controls. Considering the MAT, the pIkB/IkB ratio was significantly lower and the anti-inflammatory cytokine IL10 was significantly higher in CD when compared to controls. Finally, the protein content of pSTAT1 was higher in MAT of CD compared to controls. These findings reinforce the predominance of the proinflammatory NF-kB pathway in CD intestinal mucosa. For the first time, we showed the activation of STAT1 pathway in MAT of CD patients, which may help to understand the physiopathology of this immune mediated disease. Andressa Coope, Lívia Bitencourt Pascoal, Francesca Aparecida Ramos da Silva, José Diego Botezelli, Maria de Lourdes Setsuko Ayrizono, Marciane Milanski, Michel Gardere Camargo, Núria Planell, Mariana Portovedo, Cilene Bicca Dias, João José Fagundes, and Raquel Franco Leal Copyright © 2017 Andressa Coope et al. All rights reserved. Cytokines as Biomarkers and Their Respective Clinical Cutoff Levels Sun, 09 Apr 2017 00:00:00 +0000 Cytokines, including interleukins, interferons, tumor necrosis factors, and chemokines, have a variety of pro- and anti-inflammatory effects in the body through a number of biochemical pathways and interactions. Stimuli, actions, interactions, and downstream effects of cytokines have been investigated in more depth in recent years, and clinical research has also been conducted to implicate cytokines in causal patterns in certain diseases. However, particular cutoffs of cytokines as biomarkers for disease processes have not been well studied, and this warrants future work to potentially improve diagnoses for diseases with inflammatory markers. A limited number of studies in this area are reviewed, considering diseases correlated with abnormal cytokine profiles, as well as specific cutoffs at which cytokines have been deemed clinically useful for diagnosing those diseases through Receiver Operator Characteristics modeling. In light of studies such as those discussed in this review, cytokine testing has the potential to support diagnosis due to its lack of invasiveness and low cost, compared to other common types of testing for infections and inflammatory diseases. Rebecca N. Monastero and Srinivas Pentyala Copyright © 2017 Rebecca N. Monastero and Srinivas Pentyala. All rights reserved. Psoriatic Arthritis Is an Indicator of Significant Renal Damage in Patients with Psoriasis: An Observational and Epidemiological Study Wed, 22 Mar 2017 07:07:39 +0000 Background. Psoriasis affects joints in around 30% of the patients. Recent studies have demonstrated an increased risk of essential hypertension, ischemic heart disease, and stroke in psoriatic patients. However, the prevalence of renal disease in patients with psoriasis has not been evaluated properly. Objectives. Objectives were to evaluate renal functions in patients with psoriasis and to assess any possible relationship of renal failure with psoriasis and psoriatic arthritis. Methods. In this cross-sectional study, 30 participants were recruited into the following three groups: group-A, psoriatic arthritis; group-B, psoriasis without arthritis; and group-C, healthy subjects. Renal function tests were performed for every participant of each group. The data was analyzed by using SPSS version 16. Chi-squared and one-way ANOVA tests were applied, considering a value of less than 0.05 as a standard criterion. Results. Serum creatinine, urea, and phosphate were the highest in group-A, higher in group-B, and normal in group-C, . Similarly, GFR was the lowest in group-A, lower in group-B, and normal in group-C. The difference in mean GFR values was statistically significant, , . Moreover, proteinuria (gm/day) was seen in 96.7% of the patients with psoriatic arthritis, (, ) against 10% of the psoriatic patients without arthritis (, ). Conclusion. Derangement of renal function is more prevalent in psoriatic patients, especially in those with concomitant psoriatic arthritis. Therefore, each psoriatic patient must be routinely screened for an underlying renal failure. Abidullah Khan, Iqbal Haider, Maimoona Ayub, and Mohammad Humayun Copyright © 2017 Abidullah Khan et al. All rights reserved. HMGB1 and Histones Play a Significant Role in Inducing Systemic Inflammation and Multiple Organ Dysfunctions in Severe Acute Pancreatitis Tue, 21 Feb 2017 08:44:52 +0000 Severe acute pancreatitis (SAP) starts as a local inflammation of pancreatic tissue that induces the development of multiple extrapancreatic organs dysfunction; however, the underlying mechanisms are still not clear. Ischemia-reperfusion, circulating inflammatory cytokines, and possible bile cytokines significantly contribute to gut mucosal injury and intestinal bacterial translocation (BT) during SAP. Circulating HMGB1 level is significantly increased in SAP patients and HMGB1 is an important factor that mediates (at least partly) gut BT during SAP. Gut BT plays a critical role in triggering/inducing systemic inflammation/sepsis in critical illness, and profound systemic inflammatory response syndrome (SIRS) can lead to multiple organ dysfunction syndrome (MODS) during SAP, and systemic inflammation with multiorgan dysfunction is the cause of death in experimental SAP. Therefore, HMGB1 is an important factor that links gut BT and systemic inflammation. Furthermore, HMGB1 significantly contributes to multiple organ injuries. The SAP patients also have significantly increased circulating histones and cell-free DNAs levels, which can reflect the disease severity and contribute to multiple organ injuries in SAP. Hepatic Kupffer cells (KCs) are the predominant source of circulating inflammatory cytokines in SAP, and new evidence indicates that hepatocyte is another important source of circulating HMGB1 in SAP; therefore, treating the liver injury is important in SAP. Runkuan Yang, Jyrki Tenhunen, and Tor Inge Tonnessen Copyright © 2017 Runkuan Yang et al. All rights reserved. Sterile Neuroinflammation and Strategies for Therapeutic Intervention Tue, 03 Jan 2017 11:44:29 +0000 Sterile neuroinflammation is essential for the proper brain development and tissue repair. However, uncontrolled neuroinflammation plays a major role in the pathogenesis of various disease processes. The endogenous intracellular molecules so called damage-associated molecular patterns or alarmins or damage signals that are released by activated or necrotic cells are thought to play a crucial role in initiating an immune response. Sterile inflammatory response that occurs in Alzheimer’s disease (AD), Parkinson’s disease (PD), stroke, hemorrhage, epilepsy, or traumatic brain injury (TBI) creates a vicious cycle of unrestrained inflammation, driving progressive neurodegeneration. Neuroinflammation is a key mechanism in the progression (e.g., AD and PD) or secondary injury development (e.g., stroke, hemorrhage, stress, and TBI) of multiple brain conditions. Hence, it provides an opportunity for the therapeutic intervention to prevent progressive tissue damage and loss of function. The key for developing anti-neuroinflammatory treatment is to minimize the detrimental and neurotoxic effects of inflammation while promoting the beneficial and neurotropic effects, thereby creating ideal conditions for regeneration and repair. This review outlines how inflammation is involved in the pathogenesis of major nonpathogenic neuroinflammatory conditions and discusses the complex response of glial cells to damage signals. In addition, emerging experimental anti-neuroinflammatory drug treatment strategies are discussed. Manoj Banjara and Chaitali Ghosh Copyright © 2017 Manoj Banjara and Chaitali Ghosh. All rights reserved. Are Systematic Screening for Vitamin D Deficiency and Vitamin D Supplementation Currently Feasible for Ankylosing Spondylitis Patients? Mon, 02 Jan 2017 06:54:36 +0000 Beyond its role in calcium and phosphorus metabolism for healthy bone mineralization, there is increasing awareness for vitamin D contribution in modulation of immune reactions. Given that ankylosing spondylitis (AS) is a chronic inflammatory disease involving excess immune/inflammatory activity and posing great therapeutic challenges, it is conceivable to claim that vitamin D treatment may be a safe and effective treatment to influence or modify the primary disease and its related comorbidities. Nevertheless, consistent body of research supporting this hypothesis is still lacking. In this paper, we examine whether systematic screening and treatment for vitamin D deficiency are feasible at present. We will review the immunomodulatory role of vitamin D and its contribution in initiation and progression of AS, as well as how they would determine the occurrence of comorbid conditions. Our conclusion is that despite the overwhelmed interest about vitamin D treatment in AS patients, systematic screening and treatment for vitamin D deficiency of all AS patients are not feasible as yet. This stresses the need for further extensive well-designed research to prove vitamin D efficacy in AS beyond bone protection. And if utility is proven, personalized treatment regimes, duration of treatment, and threshold values for vitamin D should be provided. Mickael Essouma and Jean Jacques N. Noubiap Copyright © 2017 Mickael Essouma and Jean Jacques N. Noubiap. All rights reserved. Hyperexcitability in Spinal WDR Neurons following Experimental Disc Herniation Is Associated with Upregulation of Fractalkine and Its Receptor in Nucleus Pulposus and the Dorsal Root Ganglion Mon, 26 Dec 2016 12:57:15 +0000 Introduction. Lumbar radicular pain following intervertebral disc herniation may be associated with a local inflammatory response induced by nucleus pulposus (NP) cells. Methods. In anaesthetized Lewis rats, extracellular single unit recordings of wide dynamic range (WDR) neurons in the dorsal horn and qPCR were used to explore the effect of NP application onto the dorsal nerve roots (L3–L5). Results. A clear increase in C-fiber response was observed following NP conditioning. In the NP tissue, the expression of interleukin-1β (IL-1β), colony stimulating factor 1 (Csf1), fractalkine (CX3CL1), and the fractalkine receptor CX3CR1 was increased. Minocycline, an inhibitor of microglial activation, inhibited the increase in neuronal activity and attenuated the increase in IL-1β, Csf1, CX3L1, and CX3CR1 expression in NP tissue. In addition, the results demonstrated an increase in the expression of TNF, CX3CL1, and CX3CR1 in the dorsal root ganglions (DRGs). Conclusion. Hyperexcitability in the pain pathways and the local inflammation after disc herniation may involve upregulation of CX3CL1 signaling in both the NP and the DRG. Daniel Pitz Jacobsen, Aurora Moen, Fred Haugen, and Johannes Gjerstad Copyright © 2016 Daniel Pitz Jacobsen et al. All rights reserved. The Role of TLR2, TLR4, and TLR9 in the Pathogenesis of Atherosclerosis Tue, 04 Oct 2016 13:22:38 +0000 Toll-like receptors (TLRs) are key players in the pathogenesis of inflammatory conditions including coronary arterial disease (CAD). They are expressed by a variety of immune cells where they recognize pathogen-associated molecular patterns (PAMPs). TLRs recruit adaptor molecules, including myeloid differentiation primary response protein (MYD88) and TIRF-related adaptor protein (TRAM), to mediate activation of MAPKs and NF-kappa B pathways. They are associated with the development of CAD through various mechanisms. TLR4 is expressed in lipid-rich and atherosclerotic plaques. In TLR2−/− and TLR4−/− mice, atherosclerosis-associated inflammation was diminished. Moreover, TLR2 and TLR4 may induce expression of Wnt5a in advanced staged atheromatous plaque leading to activation of the inflammatory processes. TLR9 is activated by CpG motifs in nucleic acids and have been implicated in macrophage activation and the uptake of oxLDL from the circulation. Furthermore, TLR9 also stimulates interferon-α (INF-α) secretion and increases cytotoxic activity of CD4+ T-cells towards coronary artery tunica media smooth muscle cells. This review outlines the pathophysiological role of TLR2, TLR4, and TLR9 in atherosclerosis, focusing on evidence from animal models of the disease. Mohsin H. K. Roshan, Amos Tambo, and Nikolai P. Pace Copyright © 2016 Mohsin H. K. Roshan et al. All rights reserved. Inflammatory Serum Protein Profiling of Patients with Lumbar Radicular Pain One Year after Disc Herniation Wed, 11 May 2016 12:15:30 +0000 Earlier studies suggest that lumbar radicular pain following disc herniation may be associated with a local or systemic inflammatory process. In the present study, we investigated the serum inflammatory protein profile of such patients. All 45 patients were recruited from Oslo University Hospital, Ullevål, Norway, during the period 2007–2009. The new multiplex proximity extension assay (PEA) technology was used to analyze the levels of 92 proteins. Interestingly, the present data showed that patients with radicular pain 12 months after disc herniation may be different from other patients with regard to many measurable serum cytokines. Given a false discovery rate (FDR) of 0.10 and 0.05, we identified 41 and 13 proteins, respectively, which were significantly upregulated in the patients with severe pain one year after disc herniation. On the top of the list ranked by estimated increase we found C-X-C motif chemokine 5 (CXCM5; 217% increase), epidermal growth factor (EGF; 142% increase), and monocyte chemotactic protein 4 (MCP-4; 70% increase). Moreover, a clear overall difference in the serum cytokine profile between the chronic and the recovered patients was demonstrated. Thus, the present results may be important for future protein serum profiling of lumbar radicular pain patients with regard to prognosis and choice of treatment. We conclude that serum proteins may be measurable molecular markers of persistent pain after disc herniation. Aurora Moen, Anne-Li Lind, Måns Thulin, Masood Kamali-Moghaddam, Cecilie Røe, Johannes Gjerstad, and Torsten Gordh Copyright © 2016 Aurora Moen et al. All rights reserved. The Effect of Periodontitis on Expression of Interleukin-21: A Systematic Review Mon, 22 Feb 2016 13:19:46 +0000 Purpose. Inflammation and tissue breakdown are led by an array of inflammatory destructive mediators associated with initiation and progression of inflammatory diseases like periodontitis. Current evidence shows that these inflammatory mediators have a definitive role in the pathogenesis of various systemic diseases with an inflammatory component. Interleukin-21 (IL-21) has been associated with systemic diseases like rheumatoid arthritis and Crohn’s disease that follow a chronic inflammatory cascade. Similarly recent studies have associated Interleukin-21 levels with periodontitis. This systematic review was aimed to assess the levels of IL-21 in subjects with periodontitis. Methods. A complete literature search was done in PubMed, Medline, Science Direct, and Cochrane databases and Google Scholar based on the inclusion/exclusion criteria. Six relevant articles were procured. Full text was read individually by two reviewers and data extraction was done based on STROBE statement. Results. After data extraction five observational and one interventional study were obtained. All the studies showed an increased expression of IL-21 in periodontitis and the interventional study showed reduction in IL-21 levels after nonsurgical periodontal therapy (NSP). Conclusion. Interleukin-21 levels are higher in periodontitis than controls. With this limited evidence further longitudinal studies are required to consider this as a definitive inflammatory marker. Archana Mootha, Sankari Malaiappan, N. D. Jayakumar, Sheeja S. Varghese, and Julie Toby Thomas Copyright © 2016 Archana Mootha et al. All rights reserved. Association of Alanine Aminotransferase and Periodontitis: A Cross-Sectional Analysis—NHANES 2009–2012 Thu, 11 Feb 2016 12:28:54 +0000 Objective. Alanine Aminotransferase is an enzyme associated with not only liver diseases, liver conditions, and metabolic syndrome, but also inflammation. Periodontitis is associated with increased cytokines and other markers of inflammation. The purpose of this study is to determine if an independent association between Alanine Aminotransferase and periodontitis exists. Methods. Data from the 2009-2010 and 2011-2012 National Health and Nutrition Surveys (NHANES) were combined. Data concerning periodontitis and Alanine Aminotransferase were extracted and analyzed with Rao Scott Chi-square and logistic regressions. Serum Alanine Aminotransferase was dichotomized at 40 units/liter, and periodontitis was dichotomized to the presence or absence of periodontitis. Results. In bivariate Chi-square analyses, periodontitis and Alanine Aminotransferase were associated () and remained significant in unadjusted logistic regression (OR = 1.30 [95% CI: 1.02, 1.65]). However, when other known risk factors of periodontitis were included in the analyses, the relationship attenuated and failed to reach significance (adjusted OR = 1.17 [95% CI: 0.85, 1.60]). Conclusion. Our study adds to the literature a positive but attenuated association of serum Alanine Aminotransferase with periodontitis which failed to reach significance when other known, strong risk factors of periodontitis were included in the analysis. R. Constance Wiener, Usha Sambamoorthi, and Richard J. Jurevic Copyright © 2016 R. Constance Wiener et al. All rights reserved. The Pattern of Juvenile Idiopathic Arthritis in a Single Tertiary Center in Saudi Arabia Sun, 07 Feb 2016 11:10:32 +0000 Introduction. Juvenile Idiopathic Arthritis (JIA) is the most common chronic arthritis in children. Our aim is to describe demographic, clinical, and laboratory characteristics and treatment of JIA patients followed up in Pediatric Rheumatology clinic in a tertiary center in Saudi Arabia. Methods. Medical records of all patients who are followed up between January 2007 and January 2015 were retrospectively reviewed. Data were collected about demographic, clinical, and laboratory features and treatment. Results. Total patients were 82, males were 31 (37.8%), and mean age of JIA onset was 7.1 ± 3.6 yr. Mean follow-up duration was 2.67±1.6 yr. Systemic onset JIA (SoJIA) was the commonest (36.5%), followed by polyarticular in 29.2% and oligoarticular in 28%. Large and small joints are involved in 76 (92%) and 30 (36.6%), respectively. Main extra-articular feature was fever in 34 (41.4%). Uveitis was diagnosed in 7 (8.5%) and in 5 (21.7%) of oligoarticular JIA. Anemia was found in 49 (59.7%), high ESR in 45 (54.8%), and leukocytosis and thrombocytosis in 33 (40.2%). Positive ANA was found in 30 (36.5%) mainly in oligoarticular subtype as 12 (52%) patients (out of 23) had this positive test. 9 patients (10.9%) required NSAIDs only, 6 patients (7.3%) required NSAIDs and intra-articular steroids only, and 19 (23%) required NSAIDs, methotrexate, steroids, and biologics. Conclusion. SoJIA is the most common JIA subtype in our study. A population based rather than a single center study will give more details about JIA characteristics in Saudi Arabia Mohammad H. Al-Hemairi, Shatha M. Albokhari, and Mohammed A. Muzaffer Copyright © 2016 Mohammad H. Al-Hemairi et al. All rights reserved. Investigation of the Anti-Inflammatory and Analgesic Activities of Ethanol Extract of Stem Bark of Sonapatha Oroxylum indicum In Vivo Tue, 26 Jan 2016 08:03:56 +0000 Inflammation is all a pervasive phenomenon, which is elicited by the body in response to obnoxious stimuli as a protective measure. However, sustained inflammation leads to several diseases including cancer. Therefore it is necessary to neutralize inflammation. Sonapatha (Oroxylum indicum), a medicinal plant, is traditionally used as a medicine in Ayurveda and other folk systems of medicine. It is commonly used to treat inflammatory diseases including rheumatoid arthritis and asthma. Despite this fact its anti-inflammatory and analgesic effects are not evaluated scientifically. Therefore, the anti-inflammatory and analgesic activities of Sonapatha (Oroxylum indicum) were studied in Swiss albino mice by different methods. The hot plate, acetic acid, and tail immersion tests were used to evaluate the analgesic activity whereas xylene-induced ear edema and formalin induced paw edema tests were used to study the anti-inflammatory activity of Sonapatha. The administration of mice with 250 and 300 mg/kg b.wt. of O. indicum reduced pain and inflammation indicating that Sonapatha possesses analgesic and anti-inflammatory activities. The maximum analgesic and anti-inflammatory activities were observed in mice receiving 300 mg/kg b.wt. of O. indicum ethanol extract. Our study indicates that O. indicum possesses both anti-inflammatory and analgesic activities and it may be useful as an anti-inflammatory agent in the inflammation related disorders. K. Lalrinzuali, M. Vabeiryureilai, and Ganesh Chandra Jagetia Copyright © 2016 K. Lalrinzuali et al. All rights reserved. Intravenous Immunoglobulins: Mode of Action and Indications in Autoimmune and Inflammatory Dermatoses Mon, 18 Jan 2016 11:10:18 +0000 Intravenous immunoglobulins (IVIGs), a mixture of variable amounts of proteins (albumin, IgG, IgM, IgA, and IgE antibodies), as well as salt, sugar, solvents, and detergents, are successfully used to treat a variety of dermatological disorders. For decades, IVIGs have been administered for treatment of infectious diseases and immune deficiencies, since they contain natural antibodies that represent a first-line defense against pathogens. Today their indication has expanded, including the off-label therapy for a variety of autoimmune and inflammatory diseases. In dermatology, IVIGs are administered for treatment of different disorders at different therapeutic regimens, mostly with higher doses then those administered for treatment of infectious diseases. The aim of this prospective review is to highlight the indications, effectiveness, side effects, and perspectives of the systemic treatment with IVIGs for patients with severe, life-threatening, and resistant to conventional therapies autoimmune or inflammatory dermatoses. Lyubomir A. Dourmishev, Dimitrina V. Guleva, and Ljubka G. Miteva Copyright © 2016 Lyubomir A. Dourmishev et al. All rights reserved. Nicotine Inhibits Clostridium difficile Toxin A-Induced Colitis but Not Ileitis in Rats Mon, 11 Jan 2016 07:15:35 +0000 Nicotine is protective in ulcerative colitis but not Crohn’s disease of the small intestine, but little is known about the effects of nicotine on Clostridium difficile toxin A-induced enteritis. Isolated ileal or colonic segments in anesthetized rats were pretreated with nicotine bitartrate or other pharmacological agents before intraluminal injection of toxin A. After 3 hours, the treated segments were removed and inflammation was assessed. Nicotine biphasically inhibited toxin A colitis but not ileitis. Pretreatment with the nicotinic receptor antagonist, hexamethonium, blocked the effects of nicotine. Pretreating the colonic segments with hexamethonium before toxin A administration resulted in more inflammation than seen with toxin A alone, suggesting that a tonic nicotinic anti-inflammatory condition exists in the colon. Nicotine also inhibited toxin A-induced increased colonic concentrations of the TRPV1 (transient receptor potential vanilloid subtype 1) agonist, leukotriene B4 (LTB4), and release of the proinflammatory neuropeptide, substance P. Pretreatment with nicotine did not protect against direct TRPV1-mediated colitis caused by intraluminal capsaicin. Nicotinic cholinergic receptors tonically protect the colon against inflammation and nicotine inhibits toxin A colitis but not toxin A ileitis in rats in part by inhibition of toxin A-induced activation of TRPV1 by endogenous TRPV1 agonists such as LTB4. Steven R. Vigna Copyright © 2016 Steven R. Vigna. All rights reserved. EOLA1 Inhibits Lipopolysaccharide-Induced Vascular Cell Adhesion Molecule-1 Expression by Association with MT2A in ECV304 Cells Thu, 31 Dec 2015 13:41:07 +0000 Our research group firstly discovered endothelial-overexpressed lipopolysaccharide-associated factor 1 (EOLA1, GenBank number AY074889) as a lipopolysaccharide (LPS) responsive gene in ECV304 cells. The previous studies have further demonstrated the association of EOLA1 with metallothionein 2A (MT2A), while the role of EOLA1 during LPS-induced inflammatory response in ECV304 cells is unknown. In this report, we determined the subcellular localization of EOLA1 and the regulatory capacity of EOLA1 on vascular cell adhesion molecule-1 (VCAM-1) in response to LPS in ECV304 cells. Our results show that EOLA1 is broadly diffuse in the cells, and EOLA1 expression is dramatically induced by LPS. EOLA1 knockdown results in significant enhancement of LPS-induced VCAM-1 production. Consistent with this, overexpression of EOLA1 leads to the reduction of LPS-induced VCAM-1 production. Furthermore, MT2A knockdown reduces LPS-induced VCAM-1 production. Collectively, our results demonstrate a negative regulatory role of EOLA1 on LPS-induced VCAM-1 expression involving its association with MT2A in ECV304 cells. Weiling Leng, Xiaotian Lei, Hao Meng, Xinshou Ouyang, and Ziwen Liang Copyright © 2015 Weiling Leng et al. All rights reserved.