Polycystic ovarian syndrome (PCOS) is frequently characterized by obesity and metabolic diseases including hypertension, insulin resistance, and diabetes in adulthood, all leading to an increased risk of atherosclerosis. The present study aimed to evaluate serum and production of inflammatory markers in adolescent Sardinian PCOS. On the basis of HOMA findings, patients were divided into noninsulin resistant (NIR) and insulin resistant (IR), and were weight- and age-matched with healthy girls. Inflammatory cytokines (TNF-<i>&#x03B1;</i>, IL-6, Il-10, TGF-<i>&#x03B2;</i>) and lipokines (leptin, adiponectin), the reactant hs-CRP, and <i>in vitro</i> inflammatory lympho-monocyte response to microbial stimulus were evaluated. In healthy and PCOS subjects, leptin and hs-CRP were correlated with BMI, whereas adiponectin was significantly reduced in all PCOS groups. Although cytokines were similar in all groups, Interleukin-6 (IL-6) was significantly higher in IR PCOS. Moreover, in the latter group lipopolysaccharide-activated monocytes secreted significantly higher levels of IL-6 compared to NIR and control subjects. To conclude, IR PCOS displayed increased IL-6 serum levels and higher secretion in LPS-activated monocytes, whilst revealing no differences for other inflammatory cytokines. These results suggest that in PCOS patients an altered immune response to inflammatory stimuli is present in IR, likely contributing towards determining onset of a low grade inflammation.

Anna M. Fulghesu

Francesca Sanna

Sabrina Uda

Roberta  Magnini

Elaine Portoghese

Barbara Batetta

Il-6 Serum Levels and Production Is Related to an Altered Immune Response in Polycystic Ovary Syndrome Girls with Insulin Resistance

<i  >Objective</i>. To investigate whether <i  >&#x3c9;</i>-3 fatty acid could stimulate gastrointestinal motility after abdominal operation. <i  >Method</i>. Wistar rats were randomly divided into 3 group (normal saline group, intralipid group, and <i  >&#x3c9;</i>-3 fatty acid group, <svg     style="vertical-align:-0.1638pt;width:44.400002px;" id="M1" height="11.125" version="1.1" viewBox="0 0 44.400002 11.125" width="44.400002"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,10.862)"><path id="x1D45B" d="M495 86q-46 -47 -87 -72.5t-63 -25.5q-43 0 -16 107l49 210q7 34 8 50.5t-3 21t-13 4.5q-35 0 -109.5 -72.5t-115.5 -140.5q-21 -75 -38 -159q-50 -10 -76 -21l-6 8l84 340q8 35 -4 35q-17 0 -67 -46l-15 26q44 44 85.5 70.5t64.5 26.5q35 0 10 -103l-24 -98h2&#xA;q42 56 97 103.5t96 71.5q46 26 74 26q9 0 16 -2.5t14 -11.5t9.5 -24.5t-1 -44t-13.5 -68.5q-30 -117 -47 -200q-4 -19 -3.5 -25t6.5 -6q21 0 70 48z" /></g><g transform="matrix(.017,-0,0,-.017,13.305,10.862)"><path id="x3D" d="M535 323h-483v50h483v-50zM535 138h-483v50h483v-50z" /></g><g transform="matrix(.017,-0,0,-.017,28.008,10.862)"><path id="x31" d="M384 0h-275v27q67 5 81.5 18.5t14.5 68.5v385q0 38 -7.5 47.5t-40.5 10.5l-48 2v24q85 15 178 52v-521q0 -55 14.5 -68.5t82.5 -18.5v-27z" /></g><g transform="matrix(.017,-0,0,-.017,36.168,10.862)"><path id="x38" d="M249 635q70 0 116 -43t46 -105q0 -46 -28 -80q-22 -25 -80 -64q62 -35 97 -75t35 -99q0 -81 -63 -131t-135 -50q-83 0 -137.5 45.5t-54.5 123.5q0 52 45 95q29 28 89 64q-109 62 -109 155q0 66 50.5 115t128.5 49zM238 603q-42 0 -67.5 -31t-25.5 -72q0 -50 32.5 -79.5&#xA;t98.5 -62.5q61 48 61 124q0 59 -29.5 90t-69.5 31zM248 20q46 0 76.5 33.5t30.5 89.5q0 50 -39 85.5t-110 71.5q-81 -54 -81 -137q0 -67 35.5 -105t87.5 -38z" /></g>

		
	
</svg>/group) after partial caecectomy and gastrostomosis, each group was divided into 3 groups (POD1, POD3, and POD6, <svg     style="vertical-align:-0.1638pt;width:36.237499px;" id="M2" height="11.225" version="1.1" viewBox="0 0 36.237499 11.225" width="36.237499"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,10.963)"><use xlink:href="#x1D45B"/></g><g transform="matrix(.017,-0,0,-.017,13.305,10.963)"><use xlink:href="#x3D"/></g><g transform="matrix(.017,-0,0,-.017,28.008,10.963)"><path id="x36" d="M137 343l67 33q37 17 63 17q79 0 129.5 -53t50.5 -131q0 -92 -58 -156.5t-147 -64.5t-147 68t-58 182q0 63 17 119t43 95.5t61.5 72t69 52t67.5 31.5q62 22 128 33l6 -32q-56 -11 -108 -35q-149 -71 -184 -231zM227 337q-47 0 -95 -27q-6 -23 -6 -70q0 -93 36 -155.5&#xA;t96 -62.5q53 0 78 45.5t25 105.5q0 68 -35 116t-99 48z" /></g>

		
	
</svg>/group). Serum gastrin (GAS), motilin (MTL), interleukin-1 (IL-1), interleukin-6 (IL-6), tissue necrosis factor-<i  >&#x3b1;</i> (TNF-<i  >&#x3b1;</i>), cyclooxygenase-2 (COX-2), gastric emptying rate, and small bowel propulsion rate were measured. <i  >Results</i>. On POD 3, gastric emptying rate and small bowel propulsion rate in <i  >&#x3c9;</i>-3 fatty acid group were higher than those in normal saline group and intralipid group. Serum GAS and MTL levels in <i  >&#x3c9;</i>-3 fatty acid group were higher than those in normal saline group, but serum IL-1, IL-6, TNF-<i  >&#x3b1;</i>, and COX-2 levels were lower than those in normal saline group and intralipid group. <i  >Conclusion</i>. <i  >&#x3c9;</i>-3 fatty acid could accelerate the recovery of gastrointestinal mobility after abdominal operation in rats, mainly by relieving postoperative inflammation.

Qun Zhang

Jian-Chun Yu

Wei-Ming Kang

Guang-Jin Zhu

Effect of ω-3 Fatty Acid on Gastrointestinal Motility after Abdominal Operation in Rats

<i  >Introduction</i>. Physical inactivity and obesity are independent risk factors for atherosclerosis. We analyzed the immunomodulatory capacity of 10-week intensified exercise training (ET) in obese and lean athletes. Markers of the innate immune response were investigated in obese (ONE: ET&#x2264;40&#x2009;km/week) and lean athletes (LNE: ET&#x2264;40&#x2009;km/week and LE: ET&#x2265;55&#x2009;km/week). <i  >Methods</i>. Circulating dendritic cells (DC) were analyzed by flow-cytometry for BDCA-1/-2-expression. TLR-2/-4/-7 and MyD88 were analyzed by RT-PCR and Western blot. Circulating oxLDL levels were analyzed by ELISA. <i  >Results</i>. BDCA-1 expression at baseline was lower in ONE compared to both other groups (ONE 0.15&#x25;; LNE 0.27&#x25;; LE 0.33&#x25;; <svg style="vertical-align:-0.27pt;width:43.337502px;" id="M1" height="10.1" version="1.1" viewBox="0 0 43.337502 10.1" width="43.337502"  xmlns="http://www.w3.org/2000/svg">
	<g transform="matrix(1.25,0,0,-1.25,0,10.1)">
		<g transform="translate(72,-63.92)">
			<text transform="matrix(1,0,0,-1,-71.95,64.24)">
				<tspan style="font-size: 11.21px; " x="0" y="0">𝑃</tspan>
				<tspan style="font-size: 11.21px; " x="9.7621679" y="0">&lt;</tspan>
				<tspan style="font-size: 11.21px; " x="20.555471" y="0">.</tspan>
				<tspan style="font-size: 11.21px; " x="23.357471" y="0">0</tspan>
				<tspan style="font-size: 11.21px; " x="28.961472" y="0">5</tspan>
			</text>

		</g>
	</g>
</svg>), but significantly increased in ONE after training (+50&#x25;; <svg style="vertical-align:-0.27pt;width:43.337502px;" id="M2" height="10.1" version="1.1" viewBox="0 0 43.337502 10.1" width="43.337502"  xmlns="http://www.w3.org/2000/svg">
	<g transform="matrix(1.25,0,0,-1.25,0,10.1)">
		<g transform="translate(72,-63.92)">
			<text transform="matrix(1,0,0,-1,-71.95,64.24)">
				<tspan style="font-size: 11.21px; " x="0" y="0">𝑃</tspan>
				<tspan style="font-size: 11.21px; " x="9.7621679" y="0">&lt;</tspan>
				<tspan style="font-size: 11.21px; " x="20.555471" y="0">.</tspan>
				<tspan style="font-size: 11.21px; " x="23.357471" y="0">0</tspan>
				<tspan style="font-size: 11.21px; " x="28.961472" y="0">5</tspan>
			</text>

		</g>
	</g>
</svg>). In contrast, BDCA-2 expression at baseline was higher in ONE (ONE 0.25&#x25;; LNE 0.11&#x25;; LE 0.09&#x25;; <svg style="vertical-align:-0.27pt;width:43.337502px;" id="M3" height="10.1" version="1.1" viewBox="0 0 43.337502 10.1" width="43.337502"  xmlns="http://www.w3.org/2000/svg">
	<g transform="matrix(1.25,0,0,-1.25,0,10.1)">
		<g transform="translate(72,-63.92)">
			<text transform="matrix(1,0,0,-1,-71.95,64.24)">
				<tspan style="font-size: 11.21px; " x="0" y="0">𝑃</tspan>
				<tspan style="font-size: 11.21px; " x="9.7621679" y="0">&lt;</tspan>
				<tspan style="font-size: 11.21px; " x="20.555471" y="0">.</tspan>
				<tspan style="font-size: 11.21px; " x="23.357471" y="0">0</tspan>
				<tspan style="font-size: 11.21px; " x="28.961472" y="0">5</tspan>
			</text>

		</g>
	</g>
</svg>) and decreased in ONE after the 10-week training period (&#x2212;27&#x25;; <svg style="vertical-align:-0.27pt;width:43.337502px;" id="M4" height="10.1" version="1.1" viewBox="0 0 43.337502 10.1" width="43.337502"  xmlns="http://www.w3.org/2000/svg">
	<g transform="matrix(1.25,0,0,-1.25,0,10.1)">
		<g transform="translate(72,-63.92)">
			<text transform="matrix(1,0,0,-1,-71.95,64.24)">
				<tspan style="font-size: 11.21px; " x="0" y="0">𝑃</tspan>
				<tspan style="font-size: 11.21px; " x="9.7621679" y="0">&lt;</tspan>
				<tspan style="font-size: 11.21px; " x="20.555471" y="0">.</tspan>
				<tspan style="font-size: 11.21px; " x="23.357471" y="0">0</tspan>
				<tspan style="font-size: 11.21px; " x="28.961472" y="0">5</tspan>
			</text>

		</g>
	</g>
</svg>). Gene activations of TLR-4 and TLR-7 with corresponding protein increase were found for all three groups (<svg style="vertical-align:-0.27pt;width:43.337502px;" id="M5" height="9.9375" version="1.1" viewBox="0 0 43.337502 9.9375" width="43.337502"  xmlns="http://www.w3.org/2000/svg">
	<g transform="matrix(1.25,0,0,-1.25,0,9.9375)">
		<g transform="translate(72,-64.05)">
			<text transform="matrix(1,0,0,-1,-71.95,64.37)">
				<tspan style="font-size: 11.21px; " x="0" y="0">𝑃</tspan>
				<tspan style="font-size: 11.21px; " x="9.7621679" y="0">&lt;</tspan>
				<tspan style="font-size: 11.21px; " x="20.555471" y="0">.</tspan>
				<tspan style="font-size: 11.21px; " x="23.357471" y="0">0</tspan>
				<tspan style="font-size: 11.21px; " x="28.961472" y="0">1</tspan>
			</text>

		</g>
	</g>
</svg>/<svg style="vertical-align:-0.27pt;width:43.337502px;" id="M6" height="10.1" version="1.1" viewBox="0 0 43.337502 10.1" width="43.337502"  xmlns="http://www.w3.org/2000/svg">
	<g transform="matrix(1.25,0,0,-1.25,0,10.1)">
		<g transform="translate(72,-63.92)">
			<text transform="matrix(1,0,0,-1,-71.95,64.24)">
				<tspan style="font-size: 11.21px; " x="0" y="0">𝑃</tspan>
				<tspan style="font-size: 11.21px; " x="9.7621679" y="0">&lt;</tspan>
				<tspan style="font-size: 11.21px; " x="20.555471" y="0">.</tspan>
				<tspan style="font-size: 11.21px; " x="23.357471" y="0">0</tspan>
				<tspan style="font-size: 11.21px; " x="28.961472" y="0">5</tspan>
			</text>

		</g>
	</g>
</svg>) compared to pre training. A reduction of oxLDL levels was seen in ONE (&#x2212;61&#x25;; <svg style="vertical-align:-0.27pt;width:43.337502px;" id="M7" height="10.1" version="1.1" viewBox="0 0 43.337502 10.1" width="43.337502"  xmlns="http://www.w3.org/2000/svg">
	<g transform="matrix(1.25,0,0,-1.25,0,10.1)">
		<g transform="translate(72,-63.92)">
			<text transform="matrix(1,0,0,-1,-71.95,64.24)">
				<tspan style="font-size: 11.21px; " x="0" y="0">𝑃</tspan>
				<tspan style="font-size: 11.21px; " x="9.7621679" y="0">&lt;</tspan>
				<tspan style="font-size: 11.21px; " x="20.555471" y="0">.</tspan>
				<tspan style="font-size: 11.21px; " x="23.357471" y="0">0</tspan>
				<tspan style="font-size: 11.21px; " x="28.961472" y="0">5</tspan>
			</text>

		</g>
	</g>
</svg>). <i  >Conclusions</i>. Intensified exercise induces an increase of BDCA-1+ DCs and TLR-4/-7 in obese athletes. We hereby describe new immune modulatory effects, which&#x2014;through regular aerobic exercise&#x2014;modulate innate immunity and pro-inflammatory cytokines in obesity.

Thomas Nickel

Henner Hanssen

Ingrid Emslander

Verena Drexel

Gernot Hertel

Arno Schmidt-Trucks&#228;ss

Claudia Summo

Zeljka Sisic

Marius Lambert

Eva Hoster

Martin Halle

Michael Weis

Immunomodulatory Effects of Aerobic Training in Obesity

Our previous study concerning brain trauma has shown that progesterone could regulate toll-like receptor 4 (TLR4) and nuclear factor-kappa B (NF-κB) signaling pathway in the brain, which also has been proved to play important roles in early brain injury (EBI) after subarachnoid hemorrhage (SAH). The aim of the current study was to investigate whether progesterone administration modulated TLR4/NF-κB pathway signaling pathway in the brain at the early stage of SAH. All SAH animals were subjected to injection of 0.3 ml fresh arterial, non-heparinized blood into prechiasmatic cistern in 20 seconds. Male rats were given 0 or 16 mg/kg injections of progesterone at post-SAH hours 1, 6, and 24. Brain samples were extracted at 48 h after SAH. As a result, SAH could induce a strong up-regulation of TLR4, NF-κB, pro-inflammatory cytokines, MCP-1, and ICAM-1 in the cortex. Administration of progesterone following SAH could down-regulate the cortical levels of these agents related to TLR4/NF-κB signaling pathway. Post-SAH progesterone treatment significantly ameliorated the EBI, such as the clinical behavior scale, brain edema, and blood-brain barrier (BBB) impairment. It was concluded that post-SAH progesterone administration may attenuate TLR4/NF-κB signaling pathway in the rat brain following SAH.

Zhong Wang

Gang Zuo

Xiao-Yong Shi

Jian Zhang

Qi Fang

Gang Chen

Progesterone Administration Modulates Cortical TLR4/NF-κB Signaling Pathway after Subarachnoid Hemorrhage in Male Rats

This study was aimed to investigate the effect of NF-<i>κ</i>B activity on the seizure susceptibility, brain damage, and P-gp expression in kainic acid- (KA-) induced seizure rats. Male SD rats were divided into saline control group (NS group), KA induced epilepsy group (EP group), and epilepsy group intervened with NF-<i>κ</i>B inhibitor-pyrrolidine dithiocarbamate salt (PDTC group) or with dexamethasone (DEX group).  No seizures were observed in the rats of NS group. Compared with NS group, increased P-gp expression and NF-<i>κ</i>B activation in the rat brain of the EP group were observed after KA micro-injection. Both PDTC and DEX pre-treatment significantly increased the latency to grade III or V seizure onset compared to EP group but failed to show neuron-protective effect as the number of survival neurons didn't significantly differ from that in EP group.  Furthermore, PDTC pre-treatment significantly decreased P-gp expression along with NF-<i>κ</i>B activation in the hippocampus CA3 area and amygdala complex of rats compared with the EP group, implying that NF-<i>κ</i>B activation involved in the seizure susceptibility and seizure induced brain P-gp over-expression. Additionally, DEX pre-treatment only decreased P-gp expression level without inhibition of NF-<i>κ</i>B activation, suggesting NF-<i>κ</i>B independent pathway may also participate in regulating seizure induced P-gp over-expression.

Nian Yu

Qing Di

Hao Liu

Yong Hu

Ying Jiang

Yu-kui Yan

Yan-fang Zhang

Ying-dong Zhang

Nuclear Factor-Kappa B Activity Regulates Brain Expression of P-Glycoprotein in the Kainic Acid-Induced Seizure Rats

Ethnic differences in adipose tissue distribution may contribute to different chronic disease risks across ethnic groups, and adipokines may mediate the risk. In a cross-sectional study, we examined ethnic differences in adipokines and inflammatory markers as related to body mass index (BMI) among 183 premenopausal women with Caucasian and Asian ancestry. General linear models were used to estimate adjusted mean levels of leptin, adiponectin, interleukin-6, and C-reactive protein (CRP). Asian women had significantly lower serum levels of leptin, adiponectin, and CRP than Caucasian participants (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>P</mml:mi><mml:mo>≤</mml:mo><mml:mn>.01</mml:mn></mml:math>) across all levels of BMI. Among overweight and obese women, Asians showed a stronger association of CRP with leptin (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>&#x3b2;</mml:mi><mml:mo>=</mml:mo><mml:mn>1.34</mml:mn></mml:math> versus <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>&#x3b2;</mml:mi><mml:mo>=</mml:mo><mml:mn>0.64</mml:mn></mml:math>) and with adiponectin (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>&#x3b2;</mml:mi><mml:mo>=</mml:mo><mml:mo>−</mml:mo><mml:mn>0.95</mml:mn></mml:math> versus <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>&#x3b2;</mml:mi><mml:mo>=</mml:mo><mml:mo>−</mml:mo><mml:mn>0.75</mml:mn></mml:math>) than Caucasians. Compared to Caucasians of similar BMI, Asians may experience a higher chronic disease risk due to lower levels of adiponectin despite their lower levels of leptin.

Shannon M. Conroy

Weiwen Chai

Unhee Lim

Adrian A. Franke

Robert V. Cooney

Gertraud Maskarinec

Leptin, Adiponectin, and Obesity among Caucasian and Asian Women

Early onset sepsis due to group B streptococcus leads to neonatal morbidity, increased mortality, and long-term neurological deficencies. Interaction between septicemic GBS and confluent monolayers of human coronary artery endothelial cells (HCAECs) was analyzed by genome wide expression profiling. In total, 124 genes were differentially expressed (89 upregulated, 35 downregulated) based on a more than 3-fold difference to control HCAEC. Regulated genes are involved in apoptosis, hemostasis, oxidative stress response, infection, and inflammation. Regulation of selected genes and proteins identified in the gene array analysis was confirmed by Real-time RT-PCR assay (granulocyte chemotactic protein 2), ELISA (urokinase, cyclooxygenase 2, granulocyte chemotactic protein 1), and western blotting (Heme oxygenase1, BCL2 interacting protein) at various time points between 4 and 24 hours. These results indicate that GBS infection might influence signalling pathways leading to impaired function of the innate immune system and hemorrhagic and inflammatory complications during GBS sepsis.

Claudia Beyrich

Jürgen Löffler

Anna Kobsar

Christian P. Speer

Susanne Kneitz

Martin Eigenthaler

Infection of Human Coronary Artery Endothelial Cells by Group B Streptococcus  Contributes to Dysregulation of Apoptosis, Hemostasis, and Innate Immune Responses

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<p><em>Mediators of Inflammation</em> 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</p>


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<p>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.</p>


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Mediators of Inflammation - Table of contents 2011

title

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

Mediators of Inflammation