Interlukin-6 Levels Research Articles

Achillea santolina reduces serum interlukin-6 level and hyperalgesia during complete Freund's adjuvant-induced inflammation in male Wistar rats

Immune system is involved in the etiology and pathophysiologic mechanisms of inflammation. Medicinal plants are an important source of substances which are claimed to induce non-specific immunomodulatory effects. In view of this and on account of the interleukin (IL)-6's role in inflammation and pain induction, this study investigated the effects of Achillea santolina extracts on inflammation which was induced by complete Freund's adjuvant (CFA) in male Wistar rats. Both methanolic and defatted extracts prepared from aerial parts of the plant were examined. Inflammatory symptoms such as hyperalgesia and paw edema in CFA-injected rats' paw were measured by radiant heat and plethysmometer during different stages of study respectively. Serum IL-6 level was checked by rat standard enzyme-linked immunosorbent assay specific kit. The results indicated dose-related effects of methanolic extract on paw edema, hyperalgesia and serum IL-6 level reduction in rats. Methanolic extract of A. santolina exhibited significant antihyperalgesic and anti-inflammatory effects during pretreatment and short-term treatment at dose of 200 mg/kg and there was no significant difference between 200 and 400 mg/kg doses of this extract. Defatted extract did not show significant effect on CFA-induced inflammation during different stages of treatment (P>0.05). Short-term treatment with methanolic extract at dose of 200 mg/kg was more effective than indomethacin in edema, hyperalgesia and serum IL-6 level reduction (P<0.01, P<0.01 and P<0.05 respectively). These results suggest that methanolic extract of A. santolina possesses potent anti-inflammatory and immunomodulatory activities during pretreatment and short-term administration.

Foxa1 and Foxa2 regulate bile duct development in mice

COMMENTARY ON: Foxa1 and Foxa2 regulate bile duct development in mice. J Clin Invest 2009;119:1537–45. Journal of Clinical Investigation. Online by Li Z. et al. Copyright 2009 by American society for Clinical Investigation. Reprinted with permission of American Society for Clinical Investigation in the format Journal via Copyright Clearance Center . Abstract: The forkhead box proteins A1 and A2 (Foxa1 and Foxa2) are transcription factors with critical roles in establishing the developmental competence of the foregut endoderm and in initiating liver specification. Using conditional gene ablation during a later phase of liver development, we show here that deletion of both Foxa1 and Foxa2 (Foxa1/2) in the embryonic liver caused hyperplasia of the biliary tree. Abnormal bile duct formation in Foxa1/2-deficient liver was due, at least in part, to activation of IL-6 expression, a proliferative signal for cholangiocytes. The glucocorticoid receptor is a negative regulator of IL-6 transcription; in the absence of Foxa1/2, the glucocorticoid receptor failed to bind to the IL-6 promoter, causing enhanced IL-6 expression. Thus, after liver specification, Foxa1/2 are required for normal bile duct development through prevention of excess cholangiocyte proliferation. Our data suggest that Foxa1/2 function as terminators of bile duct expansion in the adult liver through inhibition of IL-6 expression.

Sasa borealis leaves extract improves insulin resistance by modulating inflammatory cytokine secretion in high fat diet-induced obese C57/BL6J mice

Obesity is considered a mild inflammatory state, and the secretion of inflammation-related cytokines rises as adipose tissue expands. Inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interlukin 6 (IL-6) and monocyte-chemoattractant protein 1 (MCP-1), are modulated by adipose tissue and known to play an important role in insulin resistance which is the common characteristics of obesity related disorders. In this study we analyzed the effects of Sasa borealis leaves extract on inflammatory cytokines and insulin resistance in diet induced obese C57/BL6J mice. The obese state was induced by a high fat diet for 20 weeks and then the mice were divided into two groups; obese control group (OBC, n = 7) and experimental group (OB-SBE, n = 7). The OBC group was fed a high fat diet and the OB-SBE group was fed a high fat diet containing 5% Sasa borealis leaves extract (SBE) for 12 weeks. We also used mice fed a standard diet as a normal control (NC, n = 7). The body weight and adipose tissue weight in the OB group were significantly higher than those in the NC group. The effects of the high fat diet were reduced by SBE treatments, and the body weight and adipose tissue deposition in the OB-SBE group were significantly decreased compared to the OBC group. The OBC group showed higher serum glucose and insulin levels which resulted in a significant increase of incremental area under the curve (IAUC) and HOMA-IR than the NC group. Also, serum leptin, TNF-α, and IL-6 levels were significantly higher in the OBC group than in the NC group. In contrast, the OB-SBE group showed a reversal in the metabolic defects, including a decrease in glucose, insulin, IAUC, HOMA-IR, TNF-α, IL-6 and leptin levels. These results suggest that BSE can suppress increased weight gain and/or fat deposition induced by a high fat diet and theses effects are accompanied by modulation of the inflammatory cytokines, TNF-α and IL-6 secretion resulting in improved insulin resistance.

Effect of local cold-pack application on systemic anabolic and inflammatory response to sprint-interval training: a prospective comparative trial

We evaluated the effect of cold ice-pack application following a brief sprint-interval training on the balance between anabolic mediators [growth hormone (GH), insulin-like growth factor-I (IGF-I), testosterone], catabolic markers (cortisol, IGFBP-1), and circulating pro [Interlukin-6 (IL-6) and IL-1β]- and anti-inflammatory cytokines [IL-1 receptor antagonist (IL-1ra)]. Twelve males, elite junior handball players performed 4 × 250 m treadmill run, at 80% of each individual’s maximal speed, followed by a rest period with and without local cold-pack application. Pre, immediately post, and 60-min post-exercise blood samples were drawn. Exercise was associated with a significant increase in IL-6, GH, IGFBP-3, and testosterone levels. Local cold-pack application was associated with significant decreases in IL-1β, IL-1ra, IGF-I, and IGFBP-3 and a greater increase of IGFBP-1 during recovery. Local ice therapy immediately following sprint-interval training was associated with greater decreases in both pro- and anti-inflammatory cytokines and anabolic hormones supporting some clinical evidence for possible negative effects on athletic performance.

Emerging Role of Endothelial and Inflammatory Markers in Preeclampsia

Objectives:Endothelial disturbance and excess inflammatory response are pathogenic mechanisms in pre-eclampsia (PE). Authors determine the clinical diagnostic role for thrombomodulin (TM), plasminogen activator inhibitor-1 (PAI-1) as endothelial markers and C-reactive protein (CRP), and interlukin-6 (IL-6) as inflammatory markers when tested independently or in combinations.Materials and methods:We conducted a retrospective study in a cohort of 185 women grouped as 80 women with PE, 55 normotensive pregnant and 50 healthy non-pregnant. Plasma levels of TM, PAI-1, CRP and IL-6 were examined using enzyme linked immunosorbent assays.Results:Median levels and the positivity rates for the investigated markers were higher in PE as compared to the other groups (P&lt; 0.0001). Using linear regression analysis, the investigated markers were significantly correlated regarding healthy nonpregnantvsPE or normotensive pregnantvsPE. The sensitivity of PAI-1 was the highest (98%) among the tested biomarkers. Combination between the investigated markers revealed absolute sensitivity (100%) and reliable specificity especially when PAI-1 was combined with CRP at 83% specificity.Conclusions:Investigated endothelial and inflammatory markers revealed sensitive diagnostic test for PE. However, coupled combination between PAI-1 with CRP showed superior both sensitivity and specificity which represent a promising new approach for detection of PE.

Emerging role of endothelial and inflammatory markers in preeclampsia.

Objectives: Endothelial disturbance and excess inflammatory response are pathogenic mechanisms in pre-eclampsia (PE). Authors determine the clinical diagnostic role for thrombomodulin (TM), plasminogen activator inhibitor-1 (PAI-1) as endothelial markers and C-reactive protein (CRP), and interlukin-6 (IL-6) as inflammatory markers when tested independently or in combinations. Materials and methods: We conducted a retrospective study in a cohort of 185 women grouped as 80 women with PE, 55 normotensive pregnant and 50 healthy non-pregnant. Plasma levels of TM, PAI-1, CRP and IL-6 were examined using enzyme linked immunosorbent assays. Results: Median levels and the positivity rates for the investigated markers were higher in PE as compared to the other groups (P < 0.0001). Using linear regression analysis, the investigated markers were significantly correlated regarding healthy nonpregnant vs PE or normotensive pregnant vs PE. The sensitivity of PAI-1 was the highest (98%) among the tested biomarkers. Combination between the investigated markers revealed absolute sensitivity (100%) and reliable specificity especially when PAI-1 was combined with CRP at 83% specificity. Conclusions: Investigated endothelial and inflammatory markers revealed sensitive diagnostic test for PE. However, coupled combination between PAI-1 with CRP showed superior both sensitivity and specificity which represent a promising new approach for detection of PE.

Nitric oxide and interlukin-6 levels in intellectual disability adults with epilepsy

Nitric oxide (NO) and interlukin-6 (IL-6) are highly reactive mediators that have been shown to play different roles in a variety of different biological process. The role of NO and IL-6 in the neuropathogenesis of brain seizures is still questionable. In order to evaluate the role of NO and IL-6 in neurological disorders such as seizures, we investigated 19 adults with intellectual disability (ID) who suffer from epilepsy and treated for convulsions. NO metabolites (NOx) and IL-6 levels in serum obtained after night-sleep were significantly high among ID individuals diagnosed with epilepsy versus ID people without epilepsy. These results indicated that NOx and IL-6 may have a pathophysiological role in convulsions. Consequently, we suggest that professionals consider chemical inhibitors that might be helpful against the function of NO and IL-6.

Internal Biliary Drainage Is Superior to External Drainage in Reversal of the Elevated Serum Endotoxin, Interlukin-2 and Interlukin-6 in Rats with Obstructive Jaundice

Backgrounds: The roles of preoperative relief of obstructive jaundice by internal or external biliary drainage in prevention of postoperative complications remain controversial. Aims: To investigate the effects of biliary drainage on reversion of the abnormal serum endotoxin, interlukin-2 (IL-2) and interlukin-6 (IL-6) in rats with obstructive jaundice. Methods: Sixty male adult Sprague-Dawley rats were randomly assigned to four groups: obstructive jaundice (OJ; n = 15) by bile duct liagation and resection for 7 days and re-operation for sham drainage for another 7 days; internal biliary drainage (ID; n = 15) by bile duct ligation and resection for 7 days and re-operation for planting a stent between the dilated bile duct and the duodenum for another 7 days; external drainage (ED; n = 15) by bile duct ligation and resection for 7 days and re-operation for exteriorizing a drainage tube from the common bile duct through the subcutaneous channel to the nape of the neck; and sham operation (SH; n = 15). On the day 7after the second operation (14 days following the first operation), the rats were succumbed and blood specimens were collected. The concentrations of serum IL-2 and IL-6 were measured with enzyme linked immunosorbent assay (ELISA) and serum endotoxin level was measured by limulus test. Results: Endotoxemia was found in rats with OJ and the concentration of serum endotoxin in jaundiced rats (42.5 ± 3.5 pg/ml) was significantly higher than that in sham operation rats (4.1 ± 2.0 pg/ml) (P<0.01). After bile duct ligation, the concentration of serum IL-6 (212.9 ± 56.5 pg/ml) was significantly increased comparing with that in sham rats (145.3 ± 38.7pg/ml) (P<0.01). The level of serum IL-2 (212.7 ± 62.4 pg/ml) was also elevated, but the difference was not statistically significant comparing with that in sham rats (183.2 ± 59.6pg/ml). After relief of the biliary obstruction by ED, the endotoxemia was reversed (6.2 ± 2.9pg/ml) (ED vs OJ, P<0.01). The levels of interlukin-6 and interlukin-2 could not be decreased, on the contrary, they were significantly increased (269.4 ± 76.2 pg/ml and 264.9 ± 62.3pg/ml respectively) (ED vs OJ, P<0.01 and P<0.05 respectively). However, internal drainage could suppressed not only the endotoxemia (4.2 ± 2.0pg/ml), but also the serum IL-6 (169.7 ± 49.1 pg/ml) and IL-2 (184.3 ± 52.4 pg/ml) (ID vs OJ, P < 0.01, P < 0.05 and P>0.05 respectively). Conclusions: Internal biliary drainage is superior to external drainage in terms of reversal of the abnormal serum endotoxin, interlukin-2 and interlukin-6 in rats with obstructive jaundice.

Increased plasma levels of cytokines after seizures in localization-related epilepsy

Experimental studies suggest increased cerebral production of inflammatory cytokines after prolonged seizures. Whether a single non-prolonged seizure in human patients is associated with activation of cytokine network is still unknown. We studied the levels of interleukin-1beta (IL-1beta), interleukin-1 receptor antagonist (IL-1ra), interlukin-6 (IL-6) and soluble IL-6 receptors (sIL-6R and Gp130) in plasma after single seizures during video-EEG recordings in patients with chronic localization-related epilepsy. The levels of IL-1ra and IL-6 were increased after seizures, whereas IL-1beta and IL-6 cytokine receptors remained unchanged. These results show that only single seizures cause activation of cytokine cascade and associated inflammatory signals. In the case of recurrent seizures, these signals may result in structural changes in the nervous tissue, which are generally associated with drug refractory epilepsy.

Correlation between levels of TNF-α and IL-6 and hematological involvement in SLE Egyptian Patients with lupus nephritis

Systemic lupus Erythematosus (SLE) is a rheumatic autoimmune disease characterized by multisystem organ involvement and by high titers of auto antibodies against several nuclear and cytoplasmic antigens. Numerous abnormalities of the cytokine network have been described in patients suffering from SLE. However the role of cytokines in different organ involvement is not yet well defined. To determine if levels of Interlukin-6 (IL-6) and Tumor necrosis factor (TNF-alpha) correlate with SLE disease activity in Egyptian SLE patients and more specifically with hematological involvement. Levels of TNF-alpha and IL-6 in serum samples from sixty individuals (40 with Systemic lupus Erythmatosus and 20 healthy controls) were determined and renal biopsies were obtained from SLE patients. Levels of TNF-alpha and IL-6 were higher in SLE patients with active compared with inactive hematological disease. Further analysis showed that this association was dependent on inverse correlation (P=0.017, r=-0.49) for IL-6 and (P=0.76, r=-.243) for TNF-alpha. The mean level of TNF-alpha and Il-6 was (766.95+/-357.82 pg/ml) and (135.4+/-54.23 pg/ml) respectively for patients with active disease while it was (314.01+/-100.87 pg/ml) and (47.33+/-18.61 pg/ml) for those with inactive disease and (172.7+/-39.19 pg/ml) and (21.15+/-10.99 pg/ml) for the healthy control group respectively. The difference was statistically significant (P=0.002). We found significant positive correlations between TNF-alpha and IL-6 and the SLE Disease Activity Index (SLEDAI) score. (r=+0.743 and +0.772 respectively). Raised level of Il-6 and TNF-alpha may influence the development of anemia in Egyptian patients with Lupus Nephritis.

Effect of Sulfur Dioxide Inhalation on Cytokine Levels in Lungs and Serum of Mice

In order to elucidate the immunotoxic mechanism exerted by sulfur dioxide (SO2), we investigated the effect of SO2, a major air pollutant, on the cytokine levels in lungs and serum of male mice. Levels of interlukin-6(IL-6), tumor necrosis factor-α (TNF-α), and transforming growth factor-β1 (TGF-β1) in lungs and serum from male mice exposed to SO2 at various concentrations were measured by the enzyme-linked immunosorbent assay. Sixty Kunming albino male mice were divided randomly into six equal groups: three groups exposed to SO2 (14.00 ± 1.25, 28.00 ± 1.98, and 56.00 ± 3.11 mg/m3, which are 5 ± 0.45, 10 ± 0.71, and 20 ± 1.11 ppm) and their respective control groups. The results were as follows: (1) For lung tissues of male mice, exposure to SO2 at 14 mg/m3 (5 ppm) caused statistically significant increase of levels of IL-6 and TNF-α (p < .05) compared with the control group; exposure at 28 mg/m3 (10 ppm) caused a statistically highly significant increase of level of IL-6 (p < .01) and a significant increase of TNF-α (p < .05); and exposure at 56 mg/m3 (20 ppm) caused no any significant increase of levels of IL-6 and TNF-α. SO2 at all concentrations tested could not cause significant change of level of TGF-β1 in lungs. (2) For serum from male mice, after exposure to SO2 at 14 mg/m3 (5 ppm), the level of TNF-α was significantly increased (p < .05) compared with the control group, but the changes of levels of IL-6 and TGF-β1 were not significant. After exposure to SO2 at 28 mg/m3 (10 ppm) and 56 mg/m3 (20 ppm), levels of IL-6 and TNF-α were increased nonsignificantly, but the level of TGF-β1 was decreased nonsignificantly. These results imply that inflammation reaction could be induced in lung tissue by SO2 inhalation and the inflammation reaction might relate to these cytokines. And determination of cytokines in lung may be more valuable than in serum when lung injury caused by SO2.