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)

Using a functioning rat thyroid cell line (FRTL-5), we studied the effects of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6) on thyroidal type I iodothyronine 5'-deiodination (I-5'-deiodination) and on the expression of I-5'-deiodinase (I-5'-D) mRNA. After 24 h incubation in medium containing 0.5 microM rT3 with a tracer amount of [125I]rT3, radioactivity of released 125I- was counted. Deiodination in live FRTL-5 cells was enhanced about three times from the basal level by the addition of TSH and was inhibited markedly by propylthiouracil and dose dependently by T4. These results suggest the suitability of this model for investigating I-5'-deiodination in live thyroid tissue. Basal and TSH-induced I-5'-deiodination were significantly inhibited by 100 ng/liter of IL-1 beta and IL-6, and the inhibitory effect of TNF-alpha was seen over 1 microgram/liter. I-5'-deiodination was restored by removal of the cytokines. TSH-induced cAMP production and (Bu)2cAMP-induced I-5'-deiodination were also inhibited by the cytokines. Catalase, dexamethasone, and indomethacin did not abolish the inhibitory effects of the cytokines. Reverse transcriptase-polymerase chain reaction (RT-PCR) revealed a marked suppression of I-5'-D mRNA expression by IL-1 beta and IL-6. We conclude that these cytokines inhibit the thyroidal type I I-5'-deiodination in the order of potency IL-1 beta > IL-6 >> TNF-alpha, probably by decreasing the I-5'-D mRNA level.(ABSTRACT TRUNCATED AT 250 WORDS)
J Interferon Cytokine Res 1995 Apr
PMID:Effects of tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 on type I iodothyronine 5'-deiodination in rat thyroid cell line, FRTL-5. 762 12

Dysregulation in cytokines has been associated with melanomas. For example, loss of growth inhibition in advanced melanomas has been associated with interleukin-6 (IL-6) expression. Because IL-6 belongs to the hematopoietic cytokine family, which includes leukemia inhibitory factor (LIF) and interleukin-11 (IL-11), we examined the possibility of coordinate expression of LIF, IL-6, and IL-11 in three human melanoma cell lines derived from primary lesions (early) and in four lines derived from metastatic tumors (advanced). All lines examined produced at least low levels of LIF and IL-11 mRNA as measured by semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR). By enzyme-linked immunosorbent assay (ELISA), two of three early and three of four advanced lines were found to secrete LIF protein. IL-11 was assayed using growth of the responsive B9/11 cell line, but only one of seven lines made a low but measurable amount of IL-11. Cytokine protein production was not strictly correlated with mRNA abundance, nor was it strongly correlated with tumor staging. Recombinant LIF and IL-11 protein had no effect on the proliferation of any of the seven lines, suggesting that they do not act as autocrine growth factors for these melanomas. Assay of IL-6, IL-11, and LIF protein in conditioned medium from early and advanced melanoma lines gave no evidence of coordinate expression of these cytokines. We conclude that LIF and IL-11 production by melanomas may have some paracrine or endocrine function in the course of melanoma progression.
J Interferon Cytokine Res 1995 May
PMID:Expression of leukemia inhibitory factor and interleukin-11 by human melanoma cell lines: LIF, IL-6, and IL-11 are not coregulated. 764 48

Intrinsic glomerular cells, especially mesangial cells, are considered to be actively involved in the pathogenesis of glomerulonephritis (GN), but the precise mechanism(s) remains elusive. We have previously demonstrated that nephritogenic IgA immune complex can stimulate human mesangial cells (HMCs) to increase their production of interleukin-1 (IL-1) and interleukin-6 (IL-6). In order to evaluate the roles of cytokines such as IL-1 and/or IL-6 and mesangial cells as mediators of renal injury in GN, we have now examined the changes of HMCs and their secreted products in vitro, after stimulation with various concentrations of IL-1 and IL-6. Cytokine-activated HMCs showed the following changes: (1) increased cell size, with intracytoplasmic vacuoles, dilated endoplasmic reticulum, increased free ribosomes and polysomes, and mitochondrial swelling; (2) increased cell proliferation, reflected in thymidine incorporation and an increased proportion of S and G2/M phase cells by cell cycle analysis; (3) enhancement of IL-6 mRNA expression in HMCs with stimulation of IL-6 alone or IL-1 plus IL-6; and (4) release of large amounts of platelet activating factor (PAF), thromboxane B2 (TxB2), and superoxide anion. Taken together, these results strongly suggest that mesangial cell proliferation and increased production of immune/chemical mediators and superoxide anion can be directly induced by IL-1 plus IL-6. These changes may lead to ongoing renal injury.
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PMID:In vitro effects of interleukins on human mesangial cells: implications for glomerulonephritis. 774

Cytokine production was measured in mice during Salmonella typhimurium sepsis and intoxication. In mice given live S. typhimurium (10 cfu/mouse), by intra-peritoneal injection, serum levels of tumour necrosis factor (TNF)-alpha and interleukin-6 increased steadily from day 1 until day 4. Interferon-gamma levels showed a transient peak on day 3. Interleukin-1-alpha levels were very low. There were high bacterial counts in the livers at day 3 and deaths occurred from day 4 onwards. Intraperitoneal injection of lipopolysaccharide or heat-killed bacteria also induced all of the cytokines, but their time of appearance and levels varied greatly. Cytokine induction by heat-killed bacteria was more marked. Endotoxaemia decreased with time during intoxication and increased during sepsis. Bioactive TNF, as measured by a cytotoxicity assay, was found only in mice given heat-killed bacteria.
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PMID:Cytokine stimulation during Salmonella typhimurium sepsis in Itys mice. 775 14

Pretreatment of animals with the adjuvant muramyl dipeptide enhances both the production of circulating tumor necrosis factor and the sensitivity to the lethal effect of a lipopolysaccharide (LPS) challenge. The present study examined the capacity of various adjuvant muramyl dipeptide derivatives to potentiate responsiveness to LPS administration. Cytokine levels in serum were determined at various time intervals after LPS administration by bioassays and immunoassays; the cytokines examined were tumor necrosis factor, interleukin-1, interleukin-6, and gamma interferon. The time course of cytokine response was not modified by the pretreatment, but most of the levels were strongly enhanced. However, of the four compounds which were found to be potent priming agents, only two caused an increased sensitivity to LPS lethality, showing that elevated titers of cytokines in serum were not correlated with host sensitization. Interestingly, previous studies have shown that these two compounds also display neurobiological properties, implying a possible role of the central nervous system in LPS lethality. However, two hydrophilic derivatives with low activity as priming agents were capable of decreasing the toxicity of LPS when given after the challenge in galactosamine-sensitized mice. These results illustrate the diversity of responses elicited by immunological priming. They raise unanswered questions on the importance of endogenous mediators in the pathophysiological alterations during toxic shock.
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PMID:Selective modulation of lipopolysaccharide-induced death and cytokine production by various muramyl peptides. 780 45

The development of antidisease immunity in children infected with Plasmodium falciparum is thought to be related to their immunologic responses to certain soluble parasite-derived exoantigens. We have assessed both cellular and humoral responses to these antigens in a cross-sectional study of a cohort of Gabonese schoolchildren who live in an area where malaria is holoendemic and perenially transmitted, in an attempt to identify immunologic markers of this early developing protective immunity. Concurrent parasitemia was found to have a significant influence on lymphoproliferative and antibody responses to the exoantigens. Individuals with higher levels of parasitemia had significantly lower proliferative and IgG isotype responses. Higher concentrations of specific IgG1 and IgG3, in particular, were associated with lower or no parasitemia, suggesting a possible protective role for these isotypes, whereas the level of IgM antibodies showed a trend towards higher concentrations in those with parasitemia, perhaps indicative of an exoantigen-induced T cell-independent response. Cytokine responses were unaffected by either the presence or the intensity of parasitemia and were dissociated from both proliferative and antibody response to the exoantigens. However, the mitogen-stimulated production of tumor-necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL)-6 was positively correlated with the corresponding lymphoproliferative responses. At the individual level, mitogen-stimulated TNF-alpha, interferon-gamma, IL-2, and IL-6 responses were positively correlated, as were mitogen- and exoantigen-induced TNF-alpha. The results are discussed in the light of current knowledge of immune responses to the exoantigens and the development of protective immunity to P. falciparum.
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PMID:Immunologic responses to soluble exoantigens of Plasmodium falciparum in Gabonese children exposed to continuous intense infection. 781 Aug 4

Leukaemia inhibitory factor (LIF) plays an important role in embryo development and implantation. We detected peak LIF activity in porcine uterine luminal fluids (ULF) at day 12 of gestation and during day 7 and 13 of the oestrous cycle. A radio-receptor competition assay showed the presence of a molecule in ULF specifically binding to human LIF receptor (LIF-R). LIF activity was partially neutralized by anti-human LIF antibody. Interleukin-6 (IL-6) activity was detected in ULF throughout the oestrous cycle and pre-implantation period. An anti-murine alpha chain (gp80) of IL-6 receptor (IL-6R) specifically neutralized this activity. LIF and IL-6 mRNA were only detected in day 11 endometrium. The presence of LIF or IL-6 in the uterine cavity has not been previously reported. Our results extend LIF production by endometrium during the oestrous cycle and pre-implantation period to another mammalian species other than mouse.
Cytokine 1994 Sep
PMID:Presence of leukaemia inhibitory factor and interleukin 6 in porcine uterine secretions prior to conceptus attachment. 782 86

Etiology and pathogenesis of inflammatory bowel disease (IBD) remain obscure. There is substantial evidence that proinflammatory cytokines such as Interleukin-1 beta (IL-1 beta), Interleukin-6 (IL-6) and Tumour Necrosis Factor-alpha (TNF-alpha) exhibit a key role in the the inflammatory process. In situ hybridisation can depict individual cells producing cytokine mRNA. We performed hybridisation with antisense probes specific for IL-1 beta, IL-6 and TNF-alpha on sections of paraffine-embedded biopsies. Specimens obtained from three control persons and six cases of Crohn's disease (CD) were investigated. Only few positive cells were found in tissue sections of control persons, clusters of lamina propria cells or epithelial cells containing cytokine mRNA were not observed. Inflammatory bowel disease tissue contained large numbers of cells producing mRNA specific for the three proinflammatory cytokines assayed. IL-1 beta, IL-6 and TNF-alpha mRNA were predominantly detected corresponding to cells of the lamina propria. Single cells containing mRNA specific for IL-6 were also found among the epithelial lining of intestinal crypts. Epithelial cells containing IL-1 beta and IL-6 mRNA were found in specimens derived from one patient with Crohn's disease. Notably, large amounts of cells containing cytokine mRNA were not only found in inflamed, but also in macroscopically normal mucosa. In conclusion, using proinflammatory cytokines as a model, we established in situ hybridisation on sections of mucosal biopsies permitting further insight into immune activation at individual cell level.
Eur Cytokine Netw
PMID:Cytokine expression in intestinal mucosal biopsies. In situ hybridisation of the mRNA for interleukin-1 beta, interleukin-6 and tumour necrosis factor-alpha in inflammatory bowel disease. 784 54

We investigated the role of human interleukin-6 (IL-6) in the regulation of the third component of complement (C3) biosynthesis by cultured rat liver epithelial cells. A natural human IL-6 (nh IL-6) preparation was shown to up-regulate C3 production, whereas an Escherichia coli-derived recombinant human IL-6 (rh IL-6) displayed no activity on C3 biosynthesis. However, the C3-stimulating activity of the nh IL-6 preparation was only partially reduced when treated with an antihuman IL-6 monoclonal antibody. Binding studies indicated that although it was devoid of any C3 stimulating activity, rh IL-6 specifically bound to hepatic cell receptors (Kd = 0.38 nM) and possessed the same binding affinity as nh IL-6. Furthermore, the substitution of natural IL-6 molecules for the recombinant IL-6 led to the recovery of the initial C3-stimulating activity. These studies demonstrated that human IL-6 alone does not stimulate rat liver epithelial cell C3 production but is able to accentuate the C3-stimulating activity of unrecognized components which are present in the nh IL-6 preparation. Human IL-6 thus appears to act as a co-factor for the up-regulation of hepatic C3 production.
Eur Cytokine Netw
PMID:Human interleukin-6 acts as a co-factor for the up-regulation of C3 production by rat liver epithelial cells. 784 57

The clinical syndrome of cachexia is characterized by anorexia, continued losses of lean body mass, and altered carbohydrate and lipid metabolism. As early as the 1930s, this "chronic wasting" syndrome had been identified as the most frequent immediate cause of death in patients with cancer [Warren: Am J Med Sci 184:610-619, 1932]. At present, controversy remains as to the benefit of supplemental parenteral or enteral feedings in the nutritional repletion of cachectic cancer patients, since only selected patient groups have demonstrated clear benefit from their administration [Copeland et al.: Cancer 43:2108-2116, 1979; Copeland et al.: Cancer Res 37:2451-2456, 1977; Terepka and Waterhouse: Am J Med 20:225-238, 1956]. Despite having these advanced nutritional modalities firmly in our therapeutic armamentarium, the progression of cachexia in the nutritionally depleted cancer patient often continues unabated, and our ability to intervene successfully remains limited. This review proposes that host: tumor interactions lead to a nonspecific inflammatory response mediated in part by the chronic production and release of proinflammatory cytokines, including interleukin-1, tumor necrosis factor alpha, interleukin-6 and interferon-gamma, which antagonize the anabolic signals associated with enteral and parenteral nutrition support. Cytokine-mediated alterations can explain the inability of adequate dietary nitrogen and calories to result in lean tissue repletion. Based on this proposal, interrupting proinflammatory cytokine production or target organ action may be an appropriate therapeutic objective to improve nutrient utilization in patients with tumors.
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PMID:Cytokine-mediated alterations in host metabolism prevent nutritional repletion in cachectic cancer patients. 784 87


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