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)

Familial hemophagocytic lymphohistiocytosis (FHL) is a frequently missed and almost uniformly fatal childhood disorder. It is characterized by fever, hepatosplenomegaly, cytopenia, coagulopathy, and hypertriglyceridemia. The pathogenesis of FHL is not known but the above clinical and laboratory findings are compatible with reported in vitro and in vivo effects of several inflammatory cytokines. We measured circulating interferon-gamma (IFN-gamma), tumor necrosis factor/cachectin (TNF), and interleukin-6 (IL-6) in nine children with FHL. During active disease, elevated IFN-gamma was detected in seven of seven children, TNF in six of six, and IL-6 in two of six children studied. Thus, important inflammatory cytokines are augmented in active FHL and may contribute to the pathogenesis of the disease. Soluble CD8 was also increased in seven of seven children, which suggests a pathophysiologic importance of cytotoxic T lymphocytes. Because FHL appears to be associated with a systemic hypercytokinemia, our results also indicate that studies of FHL may contribute to the understanding of cytokine effects in vivo. Moreover, FHL is a hereditary disorder, suggesting that the hypercytokinemia is caused by a genetic defect in cytokine regulation.
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PMID:Hypercytokinemia in familial hemophagocytic lymphohistiocytosis. 195 80

Involuntary weight loss is a common finding and one associated with increased morbidity and mortality, especially in the elderly patient. The precise mechanisms by which weight loss occurs are currently being elucidated and probably involve the actions of classic hormones as well as cytokines, such as TNF (cachectin), adipsin, and interleukin-1 and interleukin-6. The differential diagnosis of involuntary weight loss is extensive, but case studies indicate that cancer, depression, and disorders of the gastrointestinal tract may be the most common causes. In approximately 25% of cases, no cause of weight loss is found despite extensive evaluation and prolonged follow-up. In the majority of cases, history, physical examination, and limited laboratory and radiologic studies reveal the cause of weight loss, when a cause is to be found. If an initial evaluation does not identify a cause, careful follow-up rather than undirected diagnostic testing is recommended. In the treatment of patients with involuntary weight loss, the underlying medical or psychiatric cause of the weight loss should be treated first if possible. Several medications are currently being investigated for treatment of patients with weight loss.
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PMID:Involuntary weight loss. 787 92

The authors measured the peripheral blood pro-inflammatory cytokine responses (tumor necrosis factor-alpha [TNF-alpha] and interleukin-6 [IL-6]) and related end organ responses ti intraperitoneal zymosan-saline suspension over 5 days in CD-1 mice. Other indicators of local and systemic inflammation included wet:dry weight ratios of lung, liver, kidneys, spleen, and bowel; peripheral blood hematocrit, white blood cell count, and platelet count; lung myeloperoxidase activity; lung protein leak; and bacterial translocation to liver, spleen, and mesenteric lymph nodes. The initial event in responses to zymosan A injection was a sharp rise in the peripheral blood TNF-alpha level, which crested within 1 h of injection. This response was followed by a peripheral blood leukocytosis also within 1 h, and a peak lung myeloperoxidase activity within 1-2 h of injection. The maximum lung permeability index occurred 8 h after injection (zymosan, .398 +/- .019 [n = 10]; saline vehicle, .266 +/- .007 [n = 10], p < .001) followed by the maximum lung wet:dry weight ratio, which occurred 18 h after injection. The peak wet:dry weight ratios for the other organs occurred between 12 and 24 h after injection as well. Peripheral blood IL-6 maxima followed TNF-a maxima after lags of several hours. The release of pre-formed TNF-a is likely the most proximal event following injection of zymosan, and may set in motion the processes that result in end-organ injury and secondary multiple organ dysfunction, particularly activation of leukocytes. The precise roles of TNF-alpha and IL-6 in the pathogenesis of end-organ injury, however, are not addressed.
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PMID:Multiple organ dysfunction syndrome: end organ and systemic inflammatory response in a mouse model of nonseptic origin. 860 94

The cytokine interleukin-6 (IL-6) is increased in bone and bone cells by several resorptive stimuli, including parathyroid hormone (PTH), IL-1beta, and tumor necrosis factor-alpha (TNF-alpha). The current studies were designed to determine the contribution of the protein kinase C (PKC) signaling pathway to the effects of these three agents to increase IL-6 in UMR-106 rat osteoblastic cells. Cells were pretreated with vehicle (dimethylsulfoxide [DMSO]) or the phorbol ester, phorbol 12,13-dibutyrate (PDB; 300 nM) for 48 h to down-regulate phorbol-sensitive PKC isozymes. Either PTH (0.1-10 nM), IL-1beta (0.1-10 nM), or TNF-alpha (5 nM and 10 nM) was then added for 24 h in the continued presence of vehicle or PDB. PKC isozymes were visualized by Western immunoblotting and IL-6 was determined by bioassay. PDB pretreatment caused a partial down-regulation of the conventional alpha-PKC and betaI-PKC isozymes and complete down-regulation of the novel delta-isoenzyme and epsilon-isozymes but it had no effect on the atypical zeta-PKC isozyme. PDB pretreatment reduced IL-6 responses to 5 nM and 10 nM PTH by 61% and 33%, respectively, reduced IL-6 responses to 5nM and 10 nM TNF-a by 54% and 42%, respectively, and failed to inhibit the IL-6 responses to 0.1-10 nM IL-1beta. The PDB pretreatment protocol significantly enhanced PTH-stimulated cyclic adenosine monophosphate (cAMP) production. The PKC inhibitor calphostin C also decreased IL-6 responses to PTH. Thus, in this osteoblast cell line, the PKC pathway is an important component of the signaling pathway for the IL-6 production stimulated by PTH and TNF-alpha but not that from IL-1beta.
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PMID:Protein kinase C involvement in interleukin-6 production by parathyroid hormone and tumor necrosis factor-alpha in UMR-106 osteoblastic cells. 1080 18

Recently, the role of various cytokines in the pathogenesis of chronic rhinosinusitis has come under investigation. Various studies have reported increased levels of interleukin-3, interleukin-4, interleukin-5, interleukin-13, and granulocyte macrophage-colony stimulating factor in the sinonasal mucosa of patients with chronic rhinosinusitis. The present study investigated the levels of pro-inflammatory cytokines, including interleukin-1 beta (IL-1 beta), interleukin-5 (IL-5), interleukin-6 (IL-6) interleukin-8 (IL-8), and tumor necrosis factor-alpha (TNF-alpha), in the sinonasal mucosa of patients with chronic rhinosinusitis, and evaluated the response of these cytokines to oral corticosteroids. Chronic rhinosinusitis subjects (n = 15) and control subjects (n = 9) underwent nasal endoscopy and biopsy of the sinonasal mucosa. Chronic rhinosinusitis subjects were subsequently treated with a 10-day tapering dose of prednisone followed by a second sinonasal endoscopic exam and biopsy. Mucosal biopsy specimens were immunostained for IL-1 beta, IL-5, IL-6, IL-8, and TNF-a. In chronic rhinosinusitis subjects, mucosal levels of IL-1 beta, IL-6, IL-8, and TNF-alpha were significantly elevated when compared with control subjects, and levels of IL-5 demonstrated a strong trend toward elevation. In posttreatment chronic rhinosinusitis subjects, levels of IL-6 were significantly decreased when compared with pretreatment levels, and TNF-alpha levels demonstrated a significant trend toward reduction. These findings support the hypothesis that the inflammatory response in chronic rhinosinusitis is associated with elevated levels of pro-inflammatory cytokines, and suggest that oral corticosteroids may exert a beneficial effect by significantly reducing the levels of IL-6 and TNF-alpha.
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PMID:Interleukin-1 beta, interleukin-5, interleukin-6, interleukin-8, and tumor necrosis factor-alpha in chronic sinusitis: response to systemic corticosteroids. 1119 12

Cytokines are supposed to play an essential role in the regulation of the bone metabolic unit. However, information on cytokine production of primary human osteoblasts from patients with metabolic bone disease is scarce, and few attempts have been made to correlate such data to histomorphometric parameters of individual patients. We investigated 11 patients with metabolic bone disease referred to our outpatient department for bone biopsy and analyzed interleukin (IL)-1, IL-6, and TNF-alpha protein release and gene expression in primary osteoblast cultures. Compared with four controls, five patients showed normal cytokine protein release, whereas six patients showed much higher levels of interleukin-6 (26-fold) and TNF-alpha (84-fold). All three cytokines were strongly correlated concerning gene expression and/or protein levels (r = 0.72-0.96). Histomorphometric analysis of the bone samples showed that eroded surface (ES/BS) as a parameter of bone resorption was significantly associated with TNF-a. In addition, RANKL gene expression was positively associated with ES/BS and osteoclast surface (Oc.S/BS). Finally, the formation parameters osteoid volume and osteoid surface were negatively associated with TNF-alpha. In conclusion, in an in vitro-ex vivo model of bone cells obtained from a group of 11 patients with different forms of metabolic bone disease, cytokine release in conditioned medium was significantly associated with bone resorption and bone formation, as quantified by histomorphometry. TNF-alpha seemed to be the more important cytokine; its effect on bone resorption could be mediated by RANKL.
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PMID:Cytokines, osteoprotegerin, and RANKL in vitro and histomorphometric indices of bone turnover in patients with different bone diseases. 1261 38

Cytokines are biologically active low molecular weight proteins that possess several endocrine and metabolic functions and are known products of the immune system and inflammation. Several of these cytokines were shown to be independent risk factors for cerebrovascular and coronary artery disease. Because visceral and subcutaneous adipose tissues are the major sources of cytokines (adipokines), increased adipose tissue mass is associated with alteration in adipokine production (eg, overexpression of tumor necrosis factor-a, interleukin-6, plasminogen activator inhibitor-1, and underexpression of adiponectin in adipose tissue). The proinflammatory status associated with these changes provides a potential link between insulin resistance and endothelial dysfunction, the early stage in the atherosclerotic process, in obese individuals, and in type 2 diabetic patients. Reduction of adipose tissue mass through weight reduction in association with exercise reduces TNF-a, IL-6, and PAI-1, increases adiponectin, and is associated with improved insulin sensitivity and endothelial function.
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PMID:Adipokines, inflammation, and the endothelium in diabetes. 1286 91

Proinflammatory cytokines produced by monocytes, like Interleukin-6 (IL-6), Interleukin-8 (IL-8), and tumor necrosis factor (TNF-alpha) are known for their pivotal role in the initiation of the inflammatory response following cardiopulmonary bypass (CPB). Catecholamines like epinephrine (Epi) and norepinephrine (Nor) are often necessary to stabilize the cardiac function in the early postoperative period and may influence the cytokine expression in monocytes. In this study we investigated the effects of Epi and Nor on IL-6, IL-8 and TNF-alpha expression in human monocytes stimulated with lipopolysaccharide (LPS) in whole blood, analyzed intracellularly by flow cytometry. Kinetics of intracellular proinflammatory cytokine production and LPS ED(50) were obtained. To simulate different stages of inflammation in vivo, varying concentrations of LPS (0.2 ng/ml, 1 ng/ml and 10 ng/ml) were used for stimulation. After a stimulation with LPS TNF-alpha was the first produced cytokine, followed by IL-8 and IL-6. All cytokines peaked from 3 h to 6 h. Epi and Nor had comparable effects on the expression of IL-6, IL-8 and TNF-a in monocytes. Both inhibited IL-6 and TNF-alpha expression in a concentration dependent manner whereas IL-8 expression remained unchanged. We conclude that monocytes are targets for Epi and Nor concerning their cytokine expression. The inhibiting effects of Nor and Epi were almost identical for all cytokines. Cytokine expression was affected most at low LPS concentrations.
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PMID:Effect of catecholamines on intracellular cytokine synthesis in human monocytes. 1521 48

Crohn's disease and ulcerative colitis are inflammatory diseases of the gastrointestinal tract characterized by chronic relapsing inflammation and catabolism. Growth hormone/insulin-like growth factor-I axis is important in inflammatory bowel disease, because of the effects on epithelial cell kinetics, collagen deposition and immunomodulation. The potential of growth hormone as a therapeutic option in inflammatory bowel disease has been proven in various clinical settings. Acquired growth hormone resistance in inflammatory bowel disease seems to be mediated by a combination of undernutrition and active inflammation. In particular, proinflammatory cytokines, such as TNF-a and interleukin-6, have been implicated as potential mediators of growth hormone resistance. The introduction of anti-TNF-alpha monoclonal antibodies has proven very efficacious in patients with inflammatory bowel disease. By reducing cytokines levels in inflammatory cells of intestinal mucosa, infliximab could interfere with cytokine-induced growth hormone resistance. Recent in vivo data have shown that acquired growth hormone resistance in patients with inflammatory bowel disease may be reversed after the administration of anti-TNF-alpha therapy.
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PMID:Growth hormone in inflammatory bowel disease. 1649 5

The effect of in vitro exposure to low-power laser light with a power density of 0.2 mW/cm2 and a wavelength of 632.8 nm induced by helium-neon laser on the functional activity of macrophages and splenic lymphocytes was studied. If the exposure period did not exceed 60 sec, the stimulation in interleukin-2 (IL-2) and nitric oxide (NO) production, as well as an increase in the activity of natural killer cells were observed. The increase of irradiation dose by prolongation of the exposure duration up to 180 s induced a significant decrease in NO production and natural killer cell activity, but IL-2 production was not different from the control level. A remarkable decrease in interferon-gamma (IFN-gamma) production was observed following laser light exposure of cells for 60 or 180 s, whereas under lower doses (exposure for 5 or 30 sec) IFN-gamma production increased. Irradiation of isolated macrophages induced a significant stimulation of cellular tumor necrosis factor-alpha (TNF- alpha) production at all dboes used, and, what is more important, an enhancement in both TNF-a phaand interleukin-6 (IL-6) production was revealed as early as after a 5-s exposure. In this case, more prolonged exposure periods, 60 and 180 s, either did not induce changes in IL-6 production (in macrophages) or decreased IL-6 production (in lymphocytes). Thus, upon in vitro exposure of cells to extremely low-power laser light, a basic tendency was observed: short-term irradiation predominantly induced stimulation in secretory activity of cells, whereas prolongation of exposure mainly induced immunosuppression. The only exception to the rule was a change in interleukin-3 (IL-3) production, which decreased after short-time exposure, but, on the opposite, increased when the cells were exposed for 180 s. In addition, a high sensitivity to extremely low-power laser light was supported by expression of the inducible heat shock protein, Hsp70, the effect being observed at all doses used, including the exposure for 5 s. At the same time, expression of another heat shock protein, Hsp90, was somewhat reduced after irradiation of cells with laser light.
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PMID:[Effect of low-intensity laser radiation (632.8 nm) on immune cells isolated from mice]. 1680 52


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