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 etiology of ulcerative colitis (UC) and Crohn's disease (CD) remains enigmatic. Infiltrating intestinal macrophages are capable of producing the proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6). We investigated the presence of IL-6, TNF-alpha and IL-1 beta mRNA transcripts in inflammatory bowel disease (IBD), normal, and other inflammatory intestinal specimens utilizing the polymerase chain reaction (PCR). TNF-alpha mRNA levels did not very between inflammatory bowel disease and control specimens. IL-1 beta mRNA levels were highest in active UC and noninflammatory bowel disease inflammatory specimens while IL-6 mRNA levels were highest in active IBD specimens. Infiltrating T cells, macrophages, and B cells were identified as sources of IL-6 protein in inflammatory bowel disease specimens by immunofluorescent staining. IL-6 transcripts were elevated only in active inflammatory bowel disease specimens, suggesting that IL-6-mediated immune processes are ongoing in the inflammatory mucosal environment of CD and UC.
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PMID:Tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 expression in inflammatory bowel disease. 158 85

The putative role of the cytokines interleukin-6 and tumor necrosis factor in the pathophysiology of the complications and mortality after surgery in jaundiced patients was studied in a murine model. Cytokine serum levels were determined in mice with experimental biliary obstruction. As an indicator of the activation status of macrophages, cytokine release by mononuclear phagocytes obtained from such mice was assessed. Following surgery, interleukin-6 levels increased to 2 to 3 ng/ml after 3 to 4 hr, but declined rapidly afterward to levels of 60 pg/ml after 10 days. After 12 days, substantial interleukin-6 levels were observed in jaundiced mice (100 pg/ml), whereas levels in sham mice further decreased (p less than 0.001). The cytokine tumor necrosis factor was frequently present in the serum of jaundiced mice. After 22 days, when killed, all jaundiced mice showed significant tumor necrosis factor levels (p less than 0.001). This was in contrast to sham mice in which tumor necrosis factor was never detected. The presence of an activated state of macrophages in jaundiced mice was concluded from the observed high spontaneous cytokine release and significantly higher release after stimulation (p less than 0.05). The presence of circulating cytokines was discussed in the context of the postoperative complications observed in jaundiced patients.
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PMID:Cytokines tumor necrosis factor and interleukin-6 in experimental biliary obstruction in mice. 159 52

The effects of various cytokines including interleukin-1 beta, -2, and -6, tumor necrosis factor-alpha, and granulocyte-macrophage colony stimulating factor on the DNA synthesis of cultured rabbit renal cortical tubular cells were investigated. Among these cytokines, it was found that only interleukin-1 beta could stimulate the DNA synthesis of cultured renal tubular cells, while interleukin-6 mildly suppressed the DNA synthesis of such cells. Interleukin-1 beta and -6 are produced by mesangial cells. The above results suggest that these cytokines may regulate the growth of tubular cells via the urinary flow in the nephron.
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PMID:Effects of cytokines on the growth of cultured rabbit renal cortical tubular cells. 159 93

Although ATP-MgCl2 improves hepatocellular function in a nonheparinized model of trauma-hemorrhage and crystalloid resuscitation, it remains unknown whether the beneficial effects of this agent are due to downregulation of the release of the inflammatory cytokines, tumor necrosis factor (TNF), and interleukin-6 (IL-6) under those conditions. To study this, rats underwent a 5-cm laparotomy (i.e., trauma induced) and were bled to and maintained at a mean arterial pressure of 40 mm Hg until 40% of maximum bleedout volume was returned in the form of Ringer's lactate (RL). The animals were then resuscitated with four times the volume of shed blood with RL over 60 min. ATP-MgCl2 (50 mumoles/kg body weight each) or an equivalent volume of normal saline was infused intravenously for 95 min. This infusion was started during the last 15 min of RL resuscitation. Plasma levels of TNF and IL-6 were measured at 1.5 hr after the completion of resuscitation by cytokine-dependent cellular assays. Hepatic blood flow was determined by in vivo indocyanine green clearance (corrected by hepatic extraction ratio for indocyanine green), radioactive microspheres, and [3H]-galactose clearance techniques. The results indicate that the levels of circulating TNF and IL-6 increased significantly in the hemorrhaged-resuscitated animals. ATP-MgCl2 treatment, however, markedly decreased the synthesis and/or release of these cytokines to levels similar to the sham group. The markedly decreased hepatic blood flow (as determined by three different methods) and hepatic extraction ratio for indocyanine green were also restored by ATP-MgCl2 treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mechanism of the beneficial effects of ATP-MgCl2 following trauma-hemorrhage and resuscitation: downregulation of inflammatory cytokine (TNF, IL-6) release. 159 74

The time course of thromboxane B2 (TxB2), 6-keto-PGF1 alpha (stable metabolite of prostacyclin), tumor necrosis factor-alpha (TNF alpha), platelet activating factor (PAF), and interleukin-6 (IL-6) formation after three lipopolysaccharide (LPS) infusions was studied in pigs over an 18-hr, period. The Escherichia coli endotoxin W0111:B4 was injected i.v. into 10 of the test group pigs at a dose of 0.5 micrograms/kg over 30 min at 0, 5 and 10 hr of the experiment. Three pigs injected with physiological saline served as controls. At defined time points before and after each LPS administration venous blood was withdrawn (0, 15, 30, 45, 60, 120, 180 min) and plasma levels of TxB2, 6-keto-PGF 1 alpha, PAF, TNF alpha and IL-6 were determined. Pulmonary artery pressure (PAP) and cardiac output (CO) were measured every 15 min. TxB2 and PAF peaked significantly between 30 and 45 min, TNF alpha and 6-keto-PGF 1 alpha between 30 and 60 min, and IL-6 between 120 and 180 min after each LPS injection. The mediators PAF, TNF alpha and TxB2 showed a decreasing three-peak profile whereas 6-keto-PGF1 alpha exhibited an increasing one. IL-6 plasma concentrations increased after each LPS injection. The peak after the third LPS administration, however, was surprisingly low compared to the previous two. The first LPS infusion in our test group led to a significant, sustained rise in mean PAP. After recurrent LPS injections the peak in PAP was not as marked as after the first infusion, indicating the development of a tolerance towards LPS. Initially, CO showed hypodynamic values, whereas the end stage of the experiment was characterized by hyperdynamic CO levels. In conclusion, we believe this porcine model of septic shock to be one of the first large animal models to describe in detail the time-course of various important inflammatory mediators.
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PMID:Time course of various inflammatory mediators during recurrent endotoxemia. 159 96

Although interferon-gamma has been shown to effectively prime macrophages for enhanced production of tumor necrosis factor-alpha (TNF alpha), it is reasonable to assume that other cytokines present in the extracellular environment may likewise facilitate cytokine biosynthesis. For example, interleukin-6 (IL-6) is synthesized by synovial lining macrophages and fibroblasts, and has been detected (along with TNF alpha) in rheumatoid synovial effusions. Therefore, the purpose of the present study was to determine whether IL-6 influences the production of IL-1 beta and/or TNF alpha by THP-1 macrophages. Although IL-6 treatment alone resulted in only a slight increase in TNF alpha levels, administration of IL-6 followed by Sal. minnesota LPS resulted in a synergistic potentiation of TNF alpha production by THP-1 macrophages. The priming effect of IL-6 could be reversed by boiling, or by the addition of a neutralizing polyclonal antibody against IL-6. Notably, IL-6 only weakly enhanced interleukin-1 beta production. In summary, the ability of IL-6 to potentiate TNF alpha production by THP-1 macrophages may provide insight into the regulation of the cytokine network in inflammatory diseases, such as rheumatoid arthritis.
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PMID:Interleukin-6 can prime THP-1 macrophages for enhanced production of tumor necrosis factor-alpha in response to LPS. 160 43

mRNA from lungs of mice exposed to high-dose oxygen (greater than 95%) for 3 days demonstrated increased expression of the genes for tumor necrosis factor (TNF), interleukin-1, and interleukin-6 compared with mRNA from lungs of mice exposed to room air. Daily treatment of mice exposed to high-dose oxygen with an antibody to TNF improved survival compared with mice receiving a similar dose of control immunoglobulin G. Pretreatment of mice with repetitive sublethal intraperitoneal doses of recombinant human TNF for 3 days or a single intravenous dose followed by exposure to high-dose oxygen afforded a significant survival advantage compared with high-dose oxygen-exposed mice pretreated with vehicle or interleukin-1. The repetitive intraperitoneal TNF pretreatment reduced the development of interstitial pneumonitis, pulmonary edema, and lung weight gain associated with oxygen toxicity and enhanced expression of the gene for the free radical protective enzyme manganous superoxide dismutase in lung tissue, a gene that is augmented as mice are exposed to high-dose oxygen. Furthermore a single intravenous dose of TNF 24 h after oxygen exposure was still protective. The results suggest that the toxicity of oxygen therapy can be partially ameliorated by either treatment with anti-TNF antibody or pretreatment and early treatment with TNF. These findings are consistent with the hypothesis that oxygen exposure induces TNF, which causes part of the toxicity of high-dose oxygen, and that pretreatment or early treatment with TNF induces the gene for an enzyme that recently has been shown to be very effective in protecting mice from the toxicity of oxygen.
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PMID:Role of tumor necrosis factor in oxygen toxicity. 160 98

The capacity of synoviocytes to participate in inflammatory responses may be altered by the cytokine-enhanced expression of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1). To examine this possibility, the ability of selected cytokines to enhance ICAM-1 expression was examined. The data indicated that each of these cytokines (interleukin-1 beta greater than tumor necrosis factor-alpha, interferon-gamma much greater than interleukin-6) can up-regulate synoviocyte ICAM-1 expression. This can potentially increase the ability of these cells to interact with infiltrating inflammatory cells, thereby propagating immunologically mediated inflammation such as occurs in rheumatoid synovitis.
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PMID:Regulation of the expression of adhesion molecules by human synoviocytes. 160 27

While a number of clinical studies indicate that elevated serum cytokine [interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor (TNF)] levels are associated with enhanced mortality in sepsis, the time course and the role that different macrophage (M phi) populations play in releasing these cytokines remain to be determined. To study this, polymicrobial sepsis was induced in C3H/HeN mice by cecal ligation and puncture (CLP). The animals were then sacrificed at 1, 4, or 24 hr post-CLP. Blood was taken for serum cytokine level determination. Macrophages, of either peritoneal (PM phi) or alveolar (AM phi) origin, were harvested by lavage, and their innate vs. inducible cytokine productive capacities were assessed by incubation with or without endotoxin (lipopolysaccharide; LPS). Serum levels of TNF were significantly enhanced 1 hr post-CLP (CLP = 3.8 +/- 2.4* vs. sham = 0.4 +/- 0.9 U/ml; P less than 0.05 by t test). However, not until 4 hr post-CLP were marked increases in IL-6 observed (CLP = 318.0 +/- 209.0* vs. sham = 1.1 +/- 0.5 U/ml), which remained elevated through 24 hr post-CLP (CLP = 11.3 +/- 15.0* vs. sham = 0.03 +/- 0.02 U/ml). Cytokine release (IL-1, IL-6, TNF) from PM phi (without the addition of LPS) was detectable only in cells harvested 1 h following CLP. Alveolar M phi from septic mice showed little in vivo activation. Septic PM phi IL-1 and IL-6 production was markedly depressed at all time points with LPS stimulation, but TNF release remained unaltered.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Polymicrobial sepsis selectively activates peritoneal but not alveolar macrophages to release inflammatory mediators (interleukins-1 and -6 and tumor necrosis factor). 161 4

This study was designed to examine cytokine production in a group of 22 well-trained runners covering a distance of 20 km within 2 hr. After running, all participants displayed a marked granulocytosis for 7 hr. Plasma neopterin levels increased 1 hr after exercise for 24 hr. Except for interleukin-6 (IL-6), cytokines were not reliably detected in plasma but were present in urine. Already before exercise, cytokines were detected in the urine of runners when compared to sedentary controls. Directly after running, interferon-gamma and tumor necrosis factor-alpha were further elevated but rapidly declined to preexercise levels. Interleukin-1 beta and interleukin-6 increased at a slower rate after exercise but secretion into urine persisted longer until 12 and 7 hr, respectively. Interleukin-2 (IL-2) was not detected but soluble IL-2 receptors appeared in the urine directly after running. Enhanced cytokine levels were accompanied by an only low creatinin kinase increase, indicating little muscle damage. These data show that long-distance running elevates cytokine production which supports the concept that regular, but not excessive, physical exercise may be beneficial by maintaining a stimulated immune system.
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PMID:Enhanced release of cytokines, interleukin-2 receptors, and neopterin after long-distance running. 161 21


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