Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The neutrophil is an important effector cell of the host response to sepsis. Tumor necrosis factor-alpha (TNF-alpha), a cytokine mediator of the septic response, is rapidly released following endotoxemia or gram-negative bacteremia. Interleukin-6 (IL-6) is another cytokine mediator of the host response to sepsis whose role is less well understood than that of TNF-alpha. It is known to be elevated in gram-negative sepsis, where peak levels have been correlated with mortality. This study examined the effect of IL-6 alone and in combination with TNF-alpha on three neutrophil functions--CD18 adhesion receptor expression, phagocytosis, and superoxide anion generation. Neutrophils from human volunteers were incubated with amounts of IL-6 ranging from 10 to 1000 ng/ml. At a concentration of 1000 ng/ml, IL-6 increased neutrophil phagocytosis of opsonized bacteria (826 +/- 255 x 10(3) MESF vs 552 +/- 103 MESF, P < 0.05) and also increased neutrophil superoxide anion generation (18.41 +/- 1.86 vs 12.6 nmol O2-/10(6) PMN/10 min, P < 0.05). Lesser amounts of IL-6 had no effect on phagocytosis or superoxide generation. IL-6 did not increase neutrophil CD18 adhesion receptor expression. Combining IL-6 with TNF-alpha at doses of 100 ng/ml and 100 U/ml, respectively, neutrophil phagocytosis (221 +/- 455 MESF vs 552 +/- 103 MESF) and superoxide generation (23.18 +/- 1.86 vs 12.6 nmol O2-/10(6) PMN/10 min) were significantly (P < 0.05) increased above control by an amount similar to that seen with 1000 U/ml TNF-alpha alone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tumor necrosis factor-alpha and interleukin-6 selectively regulate neutrophil function in vitro. 786 62

Tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and IL-1 have been shown to stimulate the synthesis of acute-phase proteins; however, few studies have examined the effect of these cytokines on gluconeogenesis. We investigated the effects of these cytokines on gluconeogenesis in primary cultures of rat hepatocytes. Incubation of hepatocytes for 24 hours with TNF-alpha or IL-1 alpha did not affect gluconeogenesis. Hepatocytes incubated with 100 pmol/L and 1 nmol/L IL-6 had a dose-dependent increase (P < .05) in gluconeogenesis (2.6 +/- 0.1 and 3.2 +/- 0.1 pmol/10(6) cells/min, respectively) as compared with controls (2.0 +/- 0.1).
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PMID:Interleukin-6 stimulates gluconeogenesis in primary cultures of rat hepatocytes. 786 7

Serum levels of soluble intercellular adhesion molecule-1, soluble interleukin-2 receptor, and cytokines such as interleukin-3, interleukin-4, interleukin-6, tumor necrosis factor-alpha, and granulocyte-macrophage colony-stimulating factor were examined in patients with oral disorders with 20 healthy persons used as control subjects. Patients studied included 30 with squamous cell carcinoma, 26 with oral lichen planus, 20 with recurrent aphthous ulcer, 19 with acute odontogenic bacterial infection, 16 with pseudomembranous candidiasis, and 16 with herpetic gingivostomatitis. Compared with levels in control subjects, detectable serum levels of interleukin-3 (> or = 10 pg/ml) existed more frequently in pseudomembranous candidiasis (13/16), acute odontogenic bacterial infection (14/19), and squamous cell carcinoma (24/30) and of granulocyte-macrophage colony-stimulating factor (> or = 4 pg/ml) more frequently in recurrent aphthous ulcer (15/20) and squamous cell carcinoma (21/30). These cytokine levels were increased with T stage of squamous cell carcinoma. About 20 pg/ml of interleukin-4 was detected in serum from one third to one fourth of patients with oral lichen planus, recurrent aphthous ulcer, and squamous cell carcinoma. Tumor necrosis factor-alpha was hardly detected in most patients except those with oral lichen planus and squamous cell carcinoma in which about one third of the patients had more than 40 pg/ml of tumor necrosis factor-alpha in serum. More than 10 pg/ml of interleukin-6 was frequently detected in all disorders, especially recurrent aphthous ulcer (18/20), pseudomembranous candidiasis (12/16), and acute odontogenic bacterial infection (17/19).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serum cytokines, interleukin-2 receptor, and soluble intercellular adhesion molecule-1 in oral disorders. 789 9

We investigated the effect of inflammatory cytokines on the intercellular adhesion molecule-1 expression on primary cultured murine hepatocytes. Tumor necrosis factor-alpha, interferon-gamma and interleukin-1 alpha up-regulated the intercellular adhesion molecule-1 expression on hepatocytes in a dose-dependent fashion; however, interleukin-6 did not. On the basis of kinetic analysis, the expression level reached a peak 24 hr after stimulation, and both cycloheximide and actinomycin D inhibited the expression. Furthermore, T lymphocytes bind more to interferon-gamma-stimulated hepatocytes than to unstimulated hepatocytes. The binding was dependent on the concentration of interferon-gamma. The binding was also up-regulated by stimulating T lymphocytes with phorbol myristate acetate. Tumor necrosis factor-alpha and interleukin-1 alpha demonstrated the same effect as interferon-gamma, whereas interleukin-6 did not increase T-lymphocyte adhesion to the hepatocytes. The adhesion induced by interferon-gamma or tumor necrosis factor-alpha was inhibited by antibody against either intercellular adhesion molecule-1 or lymphocyte function-associated antigen-1, a ligand for intercellular adhesion molecule-1, but was not inhibited by CD44 antibodies. These results demonstrate that inflammatory lymphokines enhance the T-lymphocyte adhesion to primary cultured hepatocytes by up-regulating the intercellular adhesion molecule-1 expression on the stimulated hepatocytes by activating the de novo pathway. This mechanism may play an important role in the pathogenesis of hepatitis.
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PMID:Inflammatory cytokines up-regulate intercellular adhesion molecule-1 expression on primary cultured mouse hepatocytes and T-lymphocyte adhesion. 790 80

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

The effects of methylprednisolone and cyclophosphamide were examined in a murine model of lupus nephritis (MRL-1pr/1pr). Animals were assigned to four groups at 12 weeks of age. Mice in the control group received intraperitoneal saline solution either daily or weekly. Animals in the low-dose methylprednisolone (MPLD) group received 6 mg/kg/day intraperitoneal methylprednisolone; those in the high-dose methylprednisolone (MPHD) group received 12 mg/kg/day intraperitoneal methylprednisolone. Animals in the cyclophosphamide group received 50 mg/kg/wk intraperitoneal cyclophosphamide. Animals surviving to 24 weeks were examined. MPHD and cyclophosphamide treatments were associated with maintenance of normal glomerular filtration rates and the development of only minimal proteinuria. However, detailed morphometric evaluation of the glomerulus revealed glomerular enlargement and mesangial matrix expansion in both groups. Unlike MPHD-treated mice, cyclophosphamide-treated animals demonstrated a marked reduction in the number of osmophilic dense deposits along the glomerular capillary walls. MPLD had little effect on function, despite significant reductions in cell proliferation and anti-double-strand DNA antibodies. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) levels were dramatically increased in plasma of control animals. Treatment with methylprednisolone and cyclophosphamide dramatically reduced TNF-alpha but not IL-6. Treatment also reduced renal IL-1 beta, TNF-alpha and transforming growth factor-beta mRNA levels compared with untreated mice. Despite minimal serologic activity and preservation of renal function, neither cyclophosphamide nor methylprednisolone was able to completely suppress disease activity, as measured by increased cytokine production and glomerular structural injury. The inability of treatment to reduce IL-6 levels may explain the resistance to treatment in this model.
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PMID:Modulation of glomerular structure and function in murine lupus nephritis by methylprednisolone and cyclophosphamide. 793 Aug 70

The proinflammatory cytokines have been implicated in mediating myocardial dysfunction associated with myocardial infarction, severe congestive heart failure, and sepsis. We tested the hypothesis that cytokine levels are elevated after uncomplicated coronary artery bypass grafting and associated with episodes of postoperative myocardial ischemia and dysfunction. Coronary artery bypass grafting was performed under general anesthesia with moderate systemic hypothermia and cold-blood potassium cardioplegic solution. Tumor necrosis factor-alpha and interleukin-6 levels were determined by bioassays, and interleukin-8 levels were measured by a sandwich enzyme-linked immunosorbent assay. Myocardial function and ischemic episodes were assessed by intraoperative transesophageal echocardiography and perioperative 12-channel Holter monitoring. A total of 22 patients were studied, with no deaths or complications. Arterial tumor necrosis factor-alpha rose in a bimodal distribution, peaking at 2 and 18 to 24 hours after the operation (at 20.2 +/- 6.4 pg/ml, [mean +/- standard error of the mean]) and 5.8 +/- 1.6 pg/ml, respectively; before cardiopulmonary bypass: 0.90 +/- 0.20 pg/ml, p < 0.001 for both peaks) then progressively declined to levels before bypass. Arterial interleukin-6 was maximally elevated immediately on termination of cardiopulmonary bypass and peaked again 12 to 18 hours after cardiopulmonary bypass (at 7520 +/- 2439 pg/ml and 6216 +/- 1928 pg/ml, respectively; before bypass: 746 +/- 187 pg/ml, p < 0.0001 for both peaks). Arterial interleukin-8 levels were more variable but followed a similar pattern, peaking in the early period after cardiopulmonary bypass and again at 16 to 18 hours after the operation (at 4110 +/- 1403 pg/ml and 1760 +/- 1145 pg/ml, respectively; before bypass: 461 +/- 158, p < 0.05 for both peaks). By multivariate analysis, the aortic crossclamp time was independently predictive of postoperative cytokine levels. Left ventricular wall motion abnormalities were associated with both interleukin-6 and interleukin-8 levels, worsening scores being associated with increasing levels (for interleukin-6, p = 0.003; for interleukin-8, p = 0.05). Postoperative myocardial ischemic episodes were associated with interleukin-6 levels, six of seven (85%) patients with episodes of myocardial ischemia after a peak in interleukin-6 concentrations (p < 0.01). We conclude that proinflammatory cytokines are elevated after uncomplicated coronary revascularization and may contribute to postoperative myocardial ischemia and segmental wall motion abnormalities.
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PMID:Relationship of the proinflammatory cytokines to myocardial ischemia and dysfunction after uncomplicated coronary revascularization. 793 95

Tumor necrosis factor (TNF) is implicated in wasting syndromes and insulin resistance in chronic infection and obese-linked diabetes. TNF (10 ng/ml) inhibited adipocyte differentiation of 3T3-L1 cells, and in these TNF treated cells little insulin-stimulated glucose uptake was observed. Treatment of 3T3-L1 cells with troglitazone (1-10 microM) partially prevented this inhibitory effect of TNF on adipogenesis, and enhanced expression of C/EBP alpha and GLUT4, even in the presence of TNF. Troglitazone also prevented the inhibitory effects of interleukin-1, interleukin-6, and leukemia inhibitory factor, but not of transforming growth factor beta on adipocyte differentiation of 3T3-L1 cells. These effects might contribute to the antidiabetic effect of troglitazone in obese diabetic animals.
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PMID:Troglitazone prevents the inhibitory effects of inflammatory cytokines on insulin-induced adipocyte differentiation in 3T3-L1 cells. 795 51

As procalcitonin concentrations have been shown to be elevated in patients with septicemia and gram-negative infections in particular, we proceeded to investigate the effect of endotoxin, a product of gram-negative bacteria, on procalcitonin concentrations in normal human volunteers. Endotoxin from Escherichia coli 0113:H10:k, was injected i.v. at a dose of 4 mg/kg BW into these healthy volunteers. Blood samples were obtained before and 1, 2, 4, 6, 8, and 24 h after injection of the endotoxin. Each patient's cardiovascular and overall clinical status was monitored over this period. The patients developed chills and rigors, myalgia, and fever between 1-3 h. Tumor necrosis factor-alpha levels increased sharply at 1 h and peaked at 90 min, reaching the baseline concentration thereafter by 6 h. Interleukin-6 levels increased more gradually, peaking at 3 h and reaching the baseline concentration at 8 h. The procalcitonin concentration, which was undetectable (< 10 pg/mL) at 0, 1, and 2 h, was detectable at 4 h and peaked at 6 h, maintaining a plateau through 8 and 24 h (4 ng/mL). There was no elevation of calcitonin concentrations, which remained below 10 pg/mL, the lowest sensitivity of the assay. Procalcitonin was measured by a two-antibody immunoradiometric assay specific for this peptide, with no cross-reactivity with calcitonin, katacalcin, or calcitonin gene-related peptide. We conclude that endotoxin induces the release of procalcitonin systemically, that this increase is not associated with an increase in calcitonin, and that the increase in procalcitonin associated with septicemia in patients may be mediated through the effect of endotoxin described here. Whether procalcitonin participates in the mechanisms underlying inflammation remains to be investigated.
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PMID:Procalcitonin increase after endotoxin injection in normal subjects. 798 63

Soluble interleukin-2 receptor levels in serum may correlate with disease activity in sarcoidosis. T cells that accumulate within pulmonary sarcoid lesions may demonstrate downregulation of their T-cell receptor-CD3 complex. Tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 appear to be increased in sarcoidosis and interact with various cell types to propagate the disease process. B cells appear to play a greater role in sarcoid pathogenesis than was earlier thought, as evidenced by enhanced products of humoral immune response (ie, immunoglobulins and immune complexes). Clinically, sarcoidosis may initially present with a variety of cutaneous manifestations. Both magnetic resonance imaging and ultrasonography may be useful in evaluating the presence of abdominal sarcoidosis. J001 scintigraphy may provide a new diagnostic technique in assessing pulmonary and lymph-node involvement in sarcoid.
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PMID:Cutaneous and musculoskeletal features, diagnostic modalities, and immunopathology in sarcoidosis. 803 81


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