UNIPROT:P05231 - FACTA Search

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Query: UNIPROT:P05231 (interleukin-6)
23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Kupffer cells are known to produce tumor necrosis factor-alpha upon stimulation with endotoxin or viruses. This tumor necrosis factor-alpha synthesis is suppressed by prostaglandin E2 or dexamethasone. Using Northern blotting and reverse transcriptase-polymerase chain reaction, it is demonstrated that endotoxin-induced tumor necrosis factor-alpha synthesis is blocked by prostaglandin E2 or dibutyryl 3':5'-cyclic adenosine monophosphate on the transcriptional level. Tumor necrosis factor-alpha itself suppressed endotoxin-evoked tumor necrosis factor-alpha mRNA expression when given in a narrow time interval with lipopolysaccharide. Interleukin-10 of human or mouse origin also inhibited the synthesis of tumor necrosis factor-alpha mRNA and protein when given more than 2 h prior to the endotoxin challenge. The suppressive effect of prostaglandin E2 lasted for more than 36 h while IL-10 blocked tumor necrosis factor-alpha production for barely 24 h. Dexamethasone reduced the endotoxin-induced tumor necrosis factor-alpha mRNA formation by approximately 50% only, although it led to nearly complete inhibition of the synthesis of the mature protein. Taken together with reverse transcriptase-polymerase chain reaction data revealing significant amounts of tumor necrosis factor-alpha mRNA in resting Kupffer cells, an additional posttranscriptional regulation of tumor necrosis factor-alpha synthesis has to be assumed. Tumor necrosis factor-alpha mRNA was not induced by interferon-gamma, interleukin-1 beta or interleukin-6 (the latter two cytokines are also synthesized by Kupffer cells), but a 24-h prestimulation of liver macrophages with interferon-gamma or phorbol ester had a modest priming effect.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of the mRNA expression for tumor necrosis factor-alpha in rat liver macrophages. 793 Apr 83

Interleukin-10 is a potent macrophage-deactivating cytokine that inhibits lipopolysaccharide-induced tumor necrosis factor production. We determined the plasma levels of immunoreactive interleukin-10 in 16 patients with septic shock and in 11 patients with circulatory shock of nonseptic origin. In septic shock, interleukin-10 levels peaked during the first 24 h (median: 48 pg/ml) and decreased progressively till Day 5. In nonseptic shock, interleukin-10 plasma levels also increased during the first 24 h but to a lesser extent (median: 17 pg/ml). In septic shock patients, interleukin-10 plasma levels were positively correlated with tumor necrosis factor (r = 0.8, p = 0.01) and with parameters of shock severity including lactate levels (r = 0.56, p < 0.05) and correlated negatively with blood platelet counts (r = -0.65, p < 0.05). The decreased production of tumor necrosis factor-alpha and interleukin-6 after in vitro incubation of whole blood from septic shock patients with lipopolysaccharide was not influenced by in vitro neutralization of interleukin-10. We conclude that interleukin-10 is produced in patients with circulatory shock of septic and nonseptic origin and that the production of this anti-inflammatory cytokine during septic shock correlates positively with the intensity of the inflammatory response.
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PMID:Clinical and biological significance of interleukin-10 plasma levels in patients with septic shock. 853 71

Cardiac surgery with cardiopulmonary bypass triggers an inflammatory response involving proinflammatory cytokines such as tumor necrosis factor-alpha, interleukin-6, and interleukin-8. To elucidate the pathophysiology of this cytokine response, we explored the possible differences in cytokine responses between patients undergoing heart transplantation and those undergoing coronary artery bypass grafting. Plasma levels of tumor necrosis factor-alpha, interleukin-6, interleukin-8, and interleukin-10 were measured in eight patients undergoing heart transplantation (mean age 44 years) and eight patients undergoing coronary artery bypass grafting (mean age 61 years). Duration of cardiopulmonary bypass and ischemic time were both longer in the heart transplantation group than in the coronary artery bypass grafting group (133 +/- 26 min vs 100 +/- 31 min, p < 0.05, and 130 +/- 47 min vs 58 +/- 21 min, p < 0.005, respectively). Samples were collected before heparin administration, at aortic crossclamping and declamping, and at 0.5, 1, 1.5, 2, 4, 12, and 24 hours after declamping. Tumor necrosis factor-alpha levels were significantly higher 30 minutes after aortic declamping in the heart transplantation group than in the coronary artery bypass grafting group (68 +/- 30 vs 18 +/- 5 pg/ml, p < 0.05). Interleukin-6 and interleukin-8 levels were also significantly higher 90 minutes after declamping in patients undergoing heart transplantation than in those undergoing coronary artery bypass grafting (310 +/- 63 vs 169 +/- 24 pg/ml, p < 0.05, and 73 +/- 17 vs 24 +/- 5 pg/ml, p < 0.01, respectively). Furthermore, interleukin-6 and interleukin-8 values 90 minutes after declamping were significantly correlated with the ischemic time (r = 0.72 and r = 0.82, respectively, both p < 0.05). Interleukin-10 levels in both groups rose to reach a peak value of around 115 pg/ml 1 hour after declamping. Patients undergoing heart transplantation exhibited a second peak of tumor necrosis factor-alpha, interleukin-8, and interleukin-10 levels 12 hours after declamping, probably related to the administration of rabbit antihuman thymocyte immunoglobulin (Thymoglobuline) 3 hours after declamping. Interleukin-6 levels decreased more significantly 12 and 24 hours after declamping in patients undergoing heart transplantation, probably related to methylprednisolone therapy. In conclusion, cardiopulmonary bypass is associated with the production of both proinflammatory and antiinflammatory cytokines. The production of proinflammatory cytokines in patients undergoing heart transplantation is higher than that in patients undergoing coronary artery bypass grafting, and this increase could be related to the longer duration of ischemia in the former group. The later course of cytokine levels after heart transplantation may be further influenced by immunosuppressive therapy.
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PMID:Human cytokine responses to cardiac transplantation and coronary artery bypass grafting. 875 37

Accidental and operative trauma are able to induce a systemic reaction of the organism characterized by fever, leukocytosis, catabolism, and an activation of the coagulation system. Interleukin-6 (IL-6) has been found to be an important mediator of this acute-phase response. In this study the influence of elective craniotomy on IL-6 plasma levels was evaluated. Blood samples were obtained from 20 patients undergoing elective craniotomy for vascular or tumorous diseases of the brain. IL-6 increased significantly (p < 0.05) from the pre-operative (0(0-5.4) pg/ml) to the intraoperative (180 min after beginning of surgery) time-point (10.6 (0-18.5) pg/ml). The maximum was reached on the first postoperative morning (13.9(4.3-45.0) pg/ml). Interleukin-10 (IL-10) is an anti-inflammatory cytokine which suppresses IL-6 synthesis in vitro in various cell lines. IL-10 plasma concentrations showed no alterations throughout the study period. Epinephrine plasma concentrations increased significantly from pre-operative values (15 (0-74) pg/ml) to the postoperative time-point (57(9-459) pg/ml). A 4.5-fold increase (p < 0.05) of norepinephrine plasma concentrations was found when comparing the data obtained 60 min after beginning of surgery with the data of the first postoperative morning. In monocytes, which are a major source of plasma IL-6, an elevation of intracellular cAMP stimulates the IL-6 synthesis. The postoperative maximum of IL-6 in plasma could be due to a release of catecholamines. In conclusion this study demonstrated an elevation of IL-6 plasma concentrations during and after elective craniotomy. Increased plasma catecholamine concentrations as well as a damage in the blood-brain barrier due to the surgical trauma with a spill-over of IL-6 from brain tissue into plasma could have contributed to this result.
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PMID:Increase of interleukin-6 plasma levels after elective craniotomy: influence of interleukin-10 and catecholamines. 868 29

Interleukin-10 (IL-10), like IL-4, is known to inhibit cytokine expression in activated human monocytes. We showed that both IL-10 and IL-4 inhibit LPS-induced IL-6 mRNA and protein expression by inhibiting the transcription rate of the IL-6 gene. The strong inhibition of the IL-6 transcription rate prompted us to study the effect of IL-10 and IL-4 on the expression of transcription factors. We questioned whether or not IL-10 and IL-4 affected the expression of transcription factors that are known to be involved in the control of the IL-6 transcription rate, namely activator protein-1 (AP-1), nuclear factor IL-6 (NF-IL6), and nuclear factor kappa B (NF-kappaB). In electrophoretic mobility shift assays (EMSAs) we showed that IL-10 and IL-4 inhibited LPS-induced AP-1 binding activity. The inhibiting effect of IL-4 was slightly more pronounced than that of IL-10. Downregulation of LPS-induced AP-1 was accompanied, and thus possibly explained, by a reduced expression at mRNA level of the two major components of the AP-1 complex, namely c-fos and c-jun as determined by Northern experiments. Binding activity of NF-IL6 was also strongly inhibited by IL-4 whereas IL-10 showed no effect. NF-IL6 mRNA levels were not affected by IL-10 or IL-4, suggesting that IL-4 affects binding activity of preexisting NF-IL6. Neither IL-10 nor IL-4 inhibited LPS-induced NF-kappa B binding activity. In agreement with this finding, Northern experiments where p65 and p105 mRNA levels were determined, demonstrated that expression of these components of the NF-kappa B transcription factor were not affected by IL-10 or IL-4. Furthermore, neither IL-10 nor IL-4 showed any effect on I-kappa B mRNA expression as determined by Northern experiments. Thus, IL-10 and IL-4 similarly affect IL-6 expression. However, for IL-4 this was accompanied with a reduction of AP-1 and NF-IL6 binding activity whereas IL-10 only inhibited AP-1 binding activity.
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PMID:Effects of IL-10 and IL-4 on LPS-induced transcription factors (AP-1, NF-IL6 and NF-kappa B) which are involved in IL-6 regulation. 870 36

Alveolar macrophages are the primary source of inflammatory cytokine production in the lung. Both site-specific and differentiation-specific factors play a role in cytokine production, and regulation of this activity in alveolar macrophages is distinctly different from that of circulating blood monocytes. Interleukin-10 (IL-10) inhibits the production of inflammatory cytokines [tumor necrosis factor (TNF)-alpha, interleukin-1 (IL-1), interleukin-6 (IL-6), and interleukin-8 (IL-8)] and enhances production of interleukin-1-receptor antagonist (IL-1ra) from endotoxin-stimulated human monocytes, but the effect of IL-10 on such activity in alveolar macrophages is unknown. This study was undertaken to determine the effect of recombinant IL-10 on endotoxin-stimulated cytokine production by human alveolar macrophages. TNF, IL-1, IL-6, and IL-8 secretions were significantly (P < 0.05) stimulated by endotoxin [lipopolysaccharide (LPS)] and were all significantly (P < 0.05) inhibited (median inhibition = 43%) by IL-10 (10 ng/ml). In contrast, IL-1ra was not stimulated by LPS and basal levels were not affected by IL-10. LPS also did not significantly elevate alveolar macrophage IL-10 secretion (< 100 pg/ml) and basal levels were undetectable (< 15 pg/ml). This potent inhibitory activity of IL-10 on inflammatory cytokine production by human alveolar macrophages suggests that exogenous IL-10 may be useful in treatment of inflammatory lung diseases such as adult respiratory distress syndrome.
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PMID:Regulation of human alveolar macrophage inflammatory cytokine production by interleukin-10. 881 Oct 54

Inflammatory cytokines have been described to play a critical role in the orientation and amplification of the IgA immune response. In this study, we show that the intranasal administration of a Bordetella pertussis strain expressing the protective antigen glutathione-S-transferase of Schistosoma mansoni (Sm28GST) induced an inflammatory response in the lungs of mice, characterized by the production of inflammatory cytokines, such as Tumor Necrosis Factor alpha, Interleukin-6 and Transforming-Growth Factor beta. The production and the secretion of these cytokines in lung tissues were early and transient. Their presence was observed only during the first week after administration despite the persistence of the bacteria for 1 month. Two weeks after inoculation, Interleukin-10 secretion was detected in the lungs, which could explain the decrease in the production of inflammatory cytokines. These inflammation-regulating cytokines, induced in the lungs by the presence of the bacterial vector, could be part of the process generating the local immune response, in particular the anti-Sm28GST IgA response.
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PMID:Local transient induction of inflammatory cytokines after intranasal administration of recombinant Bordetella pertussis. 916 Mar

Interleukin-10 is an important cytokine that is involved in regulation of pro-inflammatory cytokines and T-cell responses. Interleukin-10 has been studied extensively in various preclinical and clinical models of inflammation. The most remarkable and consistently reproducible quality of IL-10 is its ability to downregulate macrophage functions. This includes inhibiting the production of pro-inflammatory cytokines such TNF-alpha, Interleukin-1, Interleukin-6 and antigen presentation by these professional antigen presenting cells. Additionally, Interleukin-10 also has effects on various other cell types of hematopoietic origin such as B-cells, neutrophils, and most importantly T-cells. Interleukin-10 has shown efficacy in several models of autoimmune disease. The present article deals with the effect of Interleukin-10 in animal models of inflammatory bowel disease and the results of phase I clinical trials in normal human volunteers and chronic active Crohn's disease patients.
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PMID:Immunomodulation of Crohn's disease by interleukin-10. 942 29

Over the past few years, evidence has accumulated that implicates proinflammatory cytokines as the mediators responsible for the escalation of acute pancreatitis into a multisystem disease. It has been shown that the degree of serum cytokine elevation, particularly the macrophage-derived cytokines interleukin-1, interleukin-6, and tumor necrosis factor-alpha, correlates with the severity and outcome of acute pancreatitis. Interleukin-10 is an anti-inflammatory cytokine that inhibits cytokine production from the macrophage. The aim of this study was to determine whether interleukin-10 would decrease both the severity of acute pancreatitis and the level of circulating proinflammatory cytokines. Ninety female mice were divided into three equal groups. Group 1 (controls) received intraperitoneal saline solution. Groups 2 and 3 received intraperitoneal cerulein (50 mg/kg/hr) for 7 hours. In addition, group 3 was given 1500 units of intraperitoneal interleukin-10, beginning 1 hour after the induction of acute pancreatitis and every 3 hours thereafter. Animals were killed at 3-hour intervals. Blood samples were obtained for serum amylase and cytokine determinations (interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha). Pancreata were dissected free and fixed in formalin for blinded histologic scoring. Interleukin-10 reduced the serum levels of interleukin-1beta, interleukin-6, tumor necrosis factor-alpha, and amylase in comparison to untreated animals with pancreatitis (P < 0.05). Pancreatic edema, necrosis, and inflammatory cell infiltrate were also reduced in those animals given interleukin-10 (P <0.05). Histologic score, serum cytokines, and amylase levels are elevated during acute pancreatitis. Interleukin-10 given therapeutically, that is, after the onset of acute pancreatitis, lessened the severity of disease, probably through inhibition of the macrophage. This was associated with a decrease in circulating cytokine levels.
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PMID:Interleukin-10 reduces circulating levels of serum cytokines in experimental pancreatitis. 983 43

The anti-inflammatory mediator interleukin-10 was investigated as a potential inhibitor of proinflammatory cytokine release in human peripheral blood monocytes activated with titanium particles. It inhibited the secretion of both tumor necrosis factor-alpha and interleukin-6 in a dose-dependent manner, with complete inhibition observed at 2 ng/ml. Co-culture experiments were performed to determine whether this cytokine may have functional importance as an inhibitor of the inflammatory response. When unstimulated lymphocytes and monocytes were co-cultured with titanium-stimulated monocytes, they significantly suppressed the secretion of both interleukin-6 and tumor necrosis factor-alpha. The inhibitory effect of these co-cultured cells could be partially blocked with the addition of an interleukin-10 neutralizing antibody. Interleukin-10 levels were measured in monocyte cultures treated with titanium particles as well as in fresh monocyte cultures treated with conditioned medium from titanium-stimulated monocytes. The latter experiments demonstrated marked stimulation of interleukin-10 secretion in conditioned medium-treated cultures, an effect that was related to the presence of tumor necrosis factor-alpha in the conditioned medium. The addition of titanium to conditioned medium-treated cultures markedly reduced the secretion of interleukin-10, suggesting that the most responsive cells are unstimulated monocytes exposed to agents released from activated monocytes. Altogether, the expression and responsiveness to interleukin-10 suggest a potential role for anti-inflammatory cytokines in regulation of the inflammatory response to wear debris.
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PMID:Interleukin-10 inhibits cytokine synthesis in monocytes stimulated by titanium particles: evidence of an anti-inflammatory regulatory pathway. 987 94

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