Article of the Year 2020
Neutrophil Extracellular Traps (NETs) and Damage-Associated Molecular Patterns (DAMPs): Two Potential Targets for COVID-19 TreatmentRead the full article
Mediators of Inflammation publishes papers on all types of inflammatory mediators, including cytokines, histamine, bradykinin, prostaglandins, leukotrienes, PAF, biological response modifiers and the family of cell adhesion-promoting molecules
Chief Editor, Professor Agrawal, is an Assistant Clinical Professor of the Division of Basic and Clinical Immunology. Dr. Agrawal's research focuses on the dendritic cells of the immune system in the context of aging and autoimmunity.
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Astaxanthin Inhibits Interleukin-6 Expression in Cerulein/Resistin-Stimulated Pancreatic Acinar Cells
Acute pancreatitis is a common clinical condition with increasing the proinflammatory mediators, including interleukin-6 (IL-6). Obesity is a negative prognostic factor in acute pancreatitis. Obese patients with acute pancreatitis have a higher systemic inflammatory response rate. Levels of serum resistin, an adipocytokine secreted by fat tissues, increase with obesity. Cerulein, a cholecystokinin analog, induces calcium (Ca2+) overload, oxidative stress, and IL-6 expression in pancreatic acinar cells, which are hallmarks of acute pancreatitis. A recent study showed that resistin aggravates the expression of inflammatory cytokines in cerulein-stimulated pancreatic acinar cells. We aimed to investigate whether resistin amplifies cerulein-induced IL-6 expression and whether astaxanthin (ASX), an antioxidant carotenoid with anti-inflammatory properties, inhibits ceruelin/resistin-induced IL-6 expression in pancreatic acinar AR42J cells. We found that resistin enhanced intracellular Ca2+ levels, NADPH oxidase activity, intracellular reactive oxygen species (ROS) production, NF-κB activity, and IL-6 expression in cerulein-stimulated AR42J cells, which were inhibited by ASX in a dose-dependent manner. The calcium chelator BAPTA-AM inhibited cerulein/resistin-induced NADPH oxidase activation and ROS production. Antioxidant N-acetyl cysteine (NAC) and ML171, a specific NADPH oxidase 1 inhibitor, suppressed cerulein/resistin-induced ROS production, NF-κB activation, and IL-6 expression. In conclusion, ASX inhibits IL-6 expression, by reducing Ca2+ overload, NADPH oxidase-mediated ROS production, and NF-κB activity in cerulein/resistin-stimulated pancreatic acinar cells. Consumption of ASX-rich foods could be beneficial for preventing or delaying the incidence of obesity-associated acute pancreatitis.
Predictive Ability of Serum IL-27 Level for Assessing Activity of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis
Serum interleukin- (IL-) 27 level has been reported to increase in patients with several autoimmune diseases; however, its significance in patients with antineutrophil cytoplasmic antibody- (ANCA-) associated vasculitis (AAV) is unknown. In this study, we investigated the associations between serum IL-27, laboratory features, and activity of AAV and evaluate the predictive ability of serum IL-27 level for disease activity. This study included 77 AAV patients, and we collected clinical and laboratory data at blood sampling. Inflammation-related variables included white blood cell, neutrophil, lymphocyte and platelet counts, serum albumin, erythrocyte sedimentation rate, and C-reactive protein levels. Serum IL-27 and IL-18 levels were measured from stored sera using Human Magnetic Luminex® assay. High disease activity of AAV was defined as the highest tertile of Birmingham vasculitis activity score (BVAS) (≥11). The mean age of the enrolled patients was 59.9 years, and 38 (49.4%) were diagnosed as microscopic polyangiitis. In the multivariable analysis, serum albumin () and serum IL-27 level () were significantly associated with BVAS. Furthermore, patients with renal manifestation exhibited higher serum IL-27 (mean 308.7 pg/mL vs. 105.8 pg/mL) and IL-18 levels (mean 376.7 pg/mL vs. 270.4 pg/mL) than those without. On applying the optimal cut-off of serum IL-27 level for predicting high activity, AAV patients with serum pg/mL had a significantly higher risk for having high disease activity than those with serum pg/mL (relative risk 3.380, 95% confidence interval 1.223, 9.345, ). These results suggest that serum IL-27 level is associated with the cross-sectional activity and the presence of renal manifestation and could be used to predict high disease activity in patients with AAV.
Posttreatment Downregulation of Type III Interferons in Patients with Acute Brucellosis
There is a limited number of clinical studies on interferon (IFN) levels in human brucellosis. The novel group of interferons, type III interferons, which consists of four IFN-λ (lambda) molecules called IFN-λ1 or interleukin-29 (IL-29), IFN-λ2 or IL-28A, IFN-λ3 or IL-28B, and IFN-λ4, is not fully known. This study is one of the first studies of IL-28A and IL-29 levels in brucellosis cases at the end of their treatment course. A total of 33 acute brucellosis patients were included in this study. We considered changes in the levels of IL-28A and IL-29 in cases with acute brucellosis before and after treatment with standard therapy that referred to the Ayatollah Rohani Hospital in Babol, northern Iran. Of 33 included patients, 22 (66.6%) were males, and 11 (33.4%) were females. The range of patients’ age was years. Serum IL-29 and IL-28A (acute form: pg/mL and pg/mL, respectively, and posttreatment: pg/mL and pg/mL, respectively) levels were elevated significantly in acute brucellosis than after treatment (). These findings indicate that considering biomarker levels in brucellosis patients may indicate the chronicity of infection. In conclusion, we suggest that IL-29 and IL-28A levels may be valuable biomarkers for follow-up patients with brucellosis.
Overexpression of TOLLIP Protects against Acute Kidney Injury after Paraquat Intoxication through Inhibiting NLRP3 Inflammasome Activation Modulated by Toll-Like Receptor 2/4 Signaling
Paraquat (PQ) can cause multiorgan failure including acute kidney injury (AKI). Our prior study showed that Toll-interacting protein (TOLLIP) protected against PQ-induced acute lung injury. However, the role of TOLLIP in PQ-induced AKI remains undefined. This study was aimed at understanding the role and mechanism of TOLLIP in AKI. Six-eight-week-old male Wistar rats were intraperitoneally injected with 25 mg/kg PQ to induce AKI for 24 h in vivo. HK-2 cells were treated with 300 μM PQ for 24 h to induce cellular injury in vitro or 300 μM PQ and 5 μM nuclear factor-κB (NF-κB) inhibitor BAY11-7082 for 24 h. Rats were infected with adenovirus carrying TOLLIP shRNA via tail vein injection and HK-2 cells with adenovirus carrying TOLLIP shRNA or TOLLIP 48 h before PQ exposure. Results showed that TOLLIP and Toll-like receptor 2/4 (TLR2/4) expressions were boosted in the kidney after PQ intoxication. The toxic effect of PQ on the kidney and HK-2 cells was exacerbated by TOLLIP knockdown, as evidenced by aggravated glomerulus and tubule injury, inflammatory infiltration, and cell apoptosis in the kidney and increased loss of cell viability and apoptotic cells in HK-2 cells. TOLLIP knockdown also enhanced PQ-induced NLR family pyrin domain-containing 3 (NLRP3) inflammasome activation in vivo and in vitro and TLR2/4-NF-κB signaling in vitro, reflected by increased contents of proinflammatory cytokines and expressions of NLRP3 inflammasome-related proteins in the kidney and HK-2 cells and expressions of TLR2, TLR4, and nuclear NF-κB p65 in HK-2 cells. However, TOLLIP overexpression inhibited PQ-induced loss of cell viability, cell apoptosis, NLRP3 inflammasome activation, and TLR2/4-NF-κB signaling in vitro. Additionally, BAY11-7082 abolished TOLLIP knockdown-induced NLRP3 inflammasome activation in vitro, indicating that TOLLIP protected against NLRP3 inflammasome activation in PQ-induced AKI through inhibiting TLR2/4-NF-κB signaling. This study highlights the importance of TOLLIP in AKI after PQ intoxication.
Elevated Serum Interleukin-23 Levels in Patients with Oral and Cutaneous Lichen Planus
Lichen planus is considered a chronic inflammatory disease which affects different sites, such as the skin, mucous membranes, hair, and nails. Based on the evidence, a complex cytokine network plays a crucial role in lichen planus pathogenesis. The study was aimed at assessing the serum IL-23 levels in the patients with cutaneous and oral lichen planus compared to healthy controls. Method. The study included 30 cutaneous lichen planus patients, 20 oral lichen planus patients, and 33 control subjects. Five milliliters of peripheral blood was obtained from each patient, and the serum was separated. IL-23 levels were determined using the ELISA kit, and the data were analyzed using the Mann–Whitney test. Results. IL-23 levels in the patient serum with oral lichen planus ( value ≤ 0.001) were significantly higher than in controls. Furthermore, there were significant differences in IL-23 serum levels in the patients with cutaneous lichen planus compared to the healthy controls ( value ≤ 0.001). Moreover, IL-23 serum levels were statistically different between patients with cutaneous lichen planus and patients with oral lichen planus ( value ≤ 0.001). Based on the mean concentration of interleukin-23, IL-23 levels were higher in the patients with oral lichen planus than in the patients with cutaneous lichen planus. Conclusions. Elevated serum IL-23 levels in the patients with oral lichen planus may indicate that IL-23 plays a crucial role in the pathogenesis of oral lichen planus. However, more research is needed with a larger sample size.
Factors Influencing the Serum Uric Acid in Gout with Cerebral Infarction
Background. Although the relationship between gout and cardiovascular has been well demonstrated, there is little information about the difference between gout with cerebrovascular disease and cardiovascular disease. In this study, the differences between gout with cerebral infarction (gout+CI) and gout with coronary heart disease (gout+CHD) and related factors that affect serum uric acid (sUA) levels in gout+CI were investigated by a cross-sectional study. Method. The patients from Jiangxi Provincial People’s Hospital with gout+CHD, gout+CI, and gout with coronary heart disease and cerebral infarction (gout+CHD+CI) between 2016 and 2020 were included in this study, and the medical record data were collected and analyzed. Results. We observed significant differences in age, drinking, hypertension, long-term use of diuretics and NSAIDs, sUA, CRE, and blood glucose in patients with gout+CHD and gout+CI. The sUA level was significantly positively correlated with smoking, CRE, and TG in the gout+CI group and was only positively correlated with CRE in the gout+CHD group and the gout+CHD+CI group (). Interestingly, the sUA level was only negatively correlated with the age and gender in the gout+CI group (). After excluding factors with no significant statistical effect, only age, gender, smoking, CRE, and TG were included in the multiple linear regression model. It suggested that smoking, CRE, and TG are positively correlated with the sUA level, while age was negatively correlated with the sUA level. Conclusions. There are many discrepancies in clinical characteristics between gout+CHD patients and gout+CI patients, especially that the factors that affect UA levels are significantly different. The data also suggested that uric acid-lowering therapy may need to be strengthened in the young gout+CI patients with a history of smoking.