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)

We detected and quantified tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) from monocytes/macrophages (M phi) in the peripheral blood of subjects from three different population groups, i.e., tuberculin-negative healthy subjects, tuberculin-positive healthy subjects, and patients with active pulmonary tuberculosis. TNF-alpha or IL-6 activity in the culture supernatant of these cells was determined by the cytotoxicity of murine L-929 cells or by enzyme-linked immunosorbent assay, respectively. Detection and enumeration of cells secreting either TNF-alpha or IL-6 were performed by an adaptation of the enzyme-linked immunospot assay. Monocytes/M phi from tuberculin-positive healthy subjects or patients with tuberculosis showed higher TNF-alpha- and IL-6-producing activities than those from tuberculin-negative healthy subjects. The number of TNF-alpha- and IL-6-secreting cells in either lipopolysaccharide- or muramyl dipeptide-stimulated mononuclear cells from tuberculin-positive healthy subjects and patients was significantly higher than that in cells from the tuberculin-negative healthy subjects.
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PMID:Increase in tumor necrosis factor alpha- and interleukin-6-secreting cells in peripheral blood mononuclear cells from subjects infected with Mycobacterium tuberculosis. 187 27

Recent studies demonstrate that several cytokines are potent modulators of steroid release from the testis. In an attempt to determine whether these agents may influence other types of secreted substances, we used plaque assays to measure the effect of interleukin-6 (IL-6), interleukin-2 (IL-2), and tumor necrosis factor alpha on transferrin (TF) release from Sertoli cells in culture. Because Sertoli cells from different parts of the tubule respond differently to modulatory factors, we used cultures obtained by microdissection from stages III-V, VII, IX-XI, and XIII of the cycle of the seminiferous epithelium. Our results revealed that each agent increased the rate of TF plaque formation from cultures of IX-XI, and XIII staged segments but not from those staged III-V and VII. Moreover, IL-6, but not the other cytokines, modified the response of Sertoli cells to another regulator, FSH. This was evidenced by our findings that pretreatment with IL-6 for 1 h resulted in FSH-induced increases in the rate of plaque formation for cells from IX-XI segments, in addition to those segments which are normally responsive without pretreatment (III-V and VII segments). Further experiments revealed that IL-6 also had a chronic influence on the proportion of TF secretors present in certain staged cultures. Treatment for 24 h with IL-6 markedly reduced the percentage of TF secretors in cultures from stage XIII segments and resulted in a slight increase in TF cells for stage VII cultures. However, no chronic influences in TF secretors were detected with either IL-2 or tumor necrosis factor alpha treatment. Our results demonstrate very clearly that certain cytokines acting in a stage specific manner have acute and/or chronic influences on the release of TF from Sertoli cells. These findings, when viewed in light of reports of the presence of these factors in the testis, suggest strongly that cytokines or cytokine-like substances, by modulating the release of Sertoli cell substances, may play an important role in testis function.
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PMID:Effects of interleukin-6, interleukin-2, and tumor necrosis factor alpha on transferrin release from Sertoli cells in culture. 190 26

We investigated the ability of staphylococcal enterotoxins A and B, exfoliative toxins A and B, and toxic shock syndrome toxin 1 to activate macrophages. All of the toxins tested had the potential to stimulate tumoricidal activity in peritoneal macrophages from lipopolysaccharide-responsive C3HeB/FeJ mice. In contrast, none of the toxins activated cytotoxicity in lipopolysaccharide-unresponsive macrophages from C3H/HeJ mice. We also studied toxin stimulation of monokine secretion. Staphylococcal enterotoxin A, toxic shock syndrome toxin 1, and both exfoliative toxins triggered C3HeB/FeJ macrophages to secrete tumor necrosis factor alpha, but enterotoxin B induced only marginal amounts of tumor necrosis factor. All of the toxins used stimulated interleukin-6 production by macrophages from both strains of mice. Nitric oxide is produced in response to the exfoliative toxins only by the lipopolysaccharide-responsive macrophages. These results suggest that macrophages respond differently to several staphylococcal exotoxins.
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PMID:Murine macrophage activation by staphylococcal exotoxins. 193 64

The production by monocytes of interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF alpha) in intensive care unit (ICU) patients with sepsis syndrome (n = 23) or noninfectious shock (n = 6) is reported. Plasma cytokines, cell-associated cytokines within freshly isolated monocytes and LPS-induced in vitro cytokine production were assessed at admission and at regular intervals during ICU stay. TNF alpha and IL-6 were the most frequently detected circulating cytokines. Despite the fact that IL-1 alpha is the main cytokine found within monocytes upon in vitro activation of cells from healthy individuals, it was very rarely detected within freshly isolated monocytes from septic patients, and levels of cell-associated IL-1 beta were lower than those of TNF alpha. Cell-associated IL-1 beta and TNF alpha were not correlated with corresponding levels in plasma. Upon LPS stimulation, we observed a profound decrease of in vitro IL-1 alpha production by monocytes in all patients, and of IL-1 beta, IL-6, and TNF alpha in septic patients. This reduced LPS-induced production of cytokines was most pronounced in patients with gram-negative infections. Finally, monocytes from survival patients, but not from nonsurvival ones recovered their capacity to produce normal amounts of cytokines upon LPS stimulation. In conclusion, our data indicate an in vivo activation of circulating monocytes during sepsis as well as in noninfectious shock and suggest that complex regulatory mechanisms can downregulate the production of cytokines by monocytes during severe infections.
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PMID:Dysregulation of in vitro cytokine production by monocytes during sepsis. 193 59

It has been proposed that certain cytokines secreted by islet-infiltrating leukocytes may be involved in the pathogenesis of insulin-dependent diabetes mellitus. Since the cytotoxic actions by the cytokines may reflect interactions with islet cell types other than the beta-cell, in this work I have investigated the effects of different combinations of various cytokines on the proliferation and hormone content and secretion by a pure insulin-producing cell population, i.e., the clonal rat insulinoma cell line RINm5F. For this purpose RINm5F cells were exposed in culture for 1-2 days to interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma) and interferon alpha (IFN-alpha) at different concentrations. It was found that IL-1 beta markedly decreased the cellular content of insulin and secretion of the hormone into the culture medium, while causing a very slight inhibition of RINm5F cell proliferation. On the other hand, IFN-gamma and IFN-alpha both elicited marked decreases in proliferation and insulin content and secretion by the insulinoma cells. IL-6 and TNF-alpha were found not to affect these parameters. No additive or synergistic effects were observed when the cytokines were added in various combinations. There was no protection against the cytotoxicity of IL-1 beta, IFN-gamma or IFN-alpha by pre-treatment with pertussis toxin. From these findings it is concluded that the cytokines IL-1 beta, IFN-gamma and IFN-alpha act in a non-synergistic fashion in suppressing RINm5F cell proliferation and hormone secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cytokines inhibit proliferation and insulin secretion by clonal rat insulinoma cells (RINm5F) non-synergistically and in a pertussis toxin-insensitive manner. 195 44

The human leukemic cell line AML-193 was tested for its proliferative response to endogenously produced autocrine factors and to a variety of cytokines and colony-stimulating factors. Cells grown in the absence of GM-CSF incorporated tritiated thymidine, and this was partially reversed by adding neutralizing anti-GM-CSF antibodies to the culture medium, suggesting that it was due, at least in part, to autocrine GM-CSF production. This was confirmed by immunopurification of a GM-CSF-like activity from cell supernatant of AML-193 cells grown in serum free medium in the absence of exogenous GM-CSF. When AML-193 cells were cultured with GM-CSF in combination with other cytokines, Interleukin-1 alpha and beta (IL-1 alpha and beta), Interleukin-3 (IL-3), Interleukin-6 (IL-6), granulocyte colony-stimulating factor (G-CSF) and tumor necrosis factor alpha (TNF alpha), none of them affected the concentration of GM-CSF required to induce 50% of maximum proliferation (D50). However, the maximum proliferation induced by GM-CSF alone was drastically decreased by IL-1 alpha, IL-1 beta and TNF alpha. Inhibition caused by exposure of the AML-193 to IL-1 for up to 24 hr was reversible, ruling out a direct cytotoxic effect.
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PMID:Growth regulation of the AML-193 leukemic cell line: evidence for autocrine production of granulocyte-macrophage colony-stimulating factor (GM-CSF), and inhibition of GM-CSF-dependent cell proliferation by interleukin-1 (IL-1) and tumor necrosis factor (TNF alpha). 199 54

Peripheral blood monocytes can be induced by stimuli such as bacterial lipopolysaccharide (LPS) to secrete an array of cytokines. We have studied the effects of interleukin 7 (IL-7) on human peripheral blood mononuclear cells (PBMC) and found that IL-7 is a relatively potent inducer of IL-6 secretion IL-6 protein levels were determined either by the B9 hybridoma growth factor assay or by enzyme-linked immunosorbent assay, and mRNA for IL-6 was analyzed by Northern hybridization. Detailed examination revealed that, among PBMC, monocytes, rather than lymphocytes, were secreting IL-6 in response to IL-7. In contrast to the low concentrations of IL-7 required to stimulate T cell growth and differentiation (as low as 0.1 ng/ml), relatively high concentrations of IL-7 were necessary to induce IL-6 secretion by monocytes (at least 10 ng/ml). An optimal concentration of IL-7 (100 ng/ml) induced monocytes to secrete 10-fold more IL-6 than an optimal concentration of IL-1 beta (10 ng/ml), and almost as much as LPS. However, significantly more IL-7 than IL-1 beta was required to induce detectable levels of IL-6. The kinetics of IL-6 secretion by monocytes were identical in response to IL-7, IL-1 beta, or LPS, with IL-6 protein detectable in culture supernatants as early as 2 h after the initiation of culture. IL-4 was found to markedly inhibit the ability of IL-7 or LPS to induce IL-6 mRNA and IL-6 secretion. In addition to promoting IL-6 production, IL-7 induced the secretion of immunoreactive IL-1 alpha, IL-1 beta, and tumor necrosis factor alpha (TNF-alpha) by monocytes. IL-7 also induced monocyte/macrophage tumoricidal activity against a human melanoma cell target, an activity that may be related to the secretion of IL-1 alpha, IL-1 beta, and TNF-alpha. Finally, we used a whole blood culture system as a bridge to in vivo analysis to demonstrate that IL-7 induces cytokine secretion in the absence of culture medium, fetal calf serum, and adherence to plastic. Our data suggest that IL-7, in addition to regulating lymphocyte growth and differentiation, has potent effects on cells of the monocytic lineage. Thus, IL-7 may be an important mediator in inflammation and in the macrophage immune response to tumors.
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PMID:Interleukin 7 induces cytokine secretion and tumoricidal activity by human peripheral blood monocytes. 200 58

Interleukin-6 (IL-6) is a multifunctional cytokine involved in the regulation of the terminal differentiation pathway of B lymphocytes. Recent reports revealed its potential role in the in vitro and in vivo growth of human multiple myeloma cells. The mechanism, however, by which IL-6 triggers proliferation of malignant plasma cells remains controversial. Using the very sensitive 7TD 1 bioassay we quantified endogenous circulating IL-6 levels in serum samples of 104 patients suffering from monoclonal gammopathies and other hematological disorders [47 with multiple myeloma (MM), 24 with monoclonal gammopathy of unknown significance (MGUS), 8 with myeloproliferative disease, and 25 suffering from low-grade non-Hodgkin's lymphoma (NHL)]. Elevated serum levels of IL-6 (greater than 5 pg/ml) were detected in 42% of the patients with MM, in 13% with MGUS, in 15% with low-grade B-NHL, and in 1 patient with T-NHL. In patients suffering from chronic myeloproliferative diseases, IL-6 levels were within the normal range. In patients with myeloma, IL-6 levels were significantly higher at advanced stages (II/III) or with progressive disease than in patients with MM stage I, MGUS, or at the plateau phase (P less than 0.01). In patients with monoclonal gammopathies including MGUS, serum IL-6 levels correlated with neopterin, tumor necrosis factor alpha and beta 2-microglobulin. An inverse correlation was found with hemoglobin levels. From these results, we propose that in myeloma patients serum IL-6 levels may reflect disease activity and tumor cell mass. The correlation with serum neopterin, a macrophage product, also suggests its origin in an activated immune system.
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PMID:Serum levels of interleukin-6 in multiple myeloma and other hematological disorders: correlation with disease activity and other prognostic parameters. 203 68

In a previous study, we demonstrated the presence of circulating interleukin-1 (IL-1) in long-term dialyzed patients and that of tumor necrosis factor alpha (TNF alpha) in both long-term and not yet dialyzed uremic patients. In the present study, we attempted to determine the respective influence of hemodialysis (HD) and uremia on the plasma level of interleukin-6 (IL-6), which shares several biological properties with IL-1 and TNF alpha, including the induction of the acute phase response of the inflammatory process. Forty-eight patients with end-stage renal failure, including 32 long-term HD patients and 16 chronic uremic patients undergoing their first dialysis session, were tested for plasma IL-6 using both biological and immunoreactive assays. Plasma IL-6 activity was significantly increased in patients with chronic renal failure (P less than 0.001) compared to its level in normal individuals. No difference was observed, however, between long-term and not yet dialyzed patients. In the patients with the most pronounced IL-6 activity, immunoreactive IL-6 levels between 60 and 150 pg/ml were detected. A monoclonal antibody (mAb) against human IL-6 inhibited the activity of plasma in the IL-6 bioassay, and a close correlation existed between the biological activity of IL-6 and its immunoreactive level. No change in plasma IL-6 was detected during the course of the first dialysis as well as subsequent sessions. Likewise, no influence of the nature (cellulosic or synthetic polyacrilonitrile) of the dialysis membrane equipping the dialyzer was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Elevated circulating levels of interleukin-6 in patients with chronic renal failure. 206 12

Previous studies have demonstrated considerable prostanoid production by cultured proliferating rat mesangial cells (MC). In this study, human mesangial cells (HMC) were examined during serum-free culture in which the cells were reversibly growth arrested and did not suffer obvious irreversible functional changes. Non-stimulated cells released 2 to 10 pg/24 hr/micrograms cellular protein of PGE2, PGF2 alpha, 6-keto-PGF1 alpha, while TXB2 was not detectable. Stimulation with interleukin-1 beta (IL-1 beta) or tumor necrosis factor alpha (TNF alpha) induced up to 18-fold (IL-1 beta) or up to fourfold (TNF alpha) increases of prostanoid release. Combinations of the two monokines resulted in significant synergistic induction of PGE2 and 6-keto-PGF1 alpha up to 38 times that of control cells. Interleukin-6 (IL-6) and the HMC-mitogen, platelet-derived growth factor-BB (PDGF-BB) only induced marginal increases in HMC prostanoid generation. However, when PDGF-BB or -AB was combined with IL-1 beta or IL-6, prostanoid generation by HMC was synergistically increased up to 222-fold (IL-1 beta) or 12-fold (IL-6) above the control values, with the induction of PGE2 greater than 6-keto-PGF1 alpha greater than PGF2 alpha much greater than TXB2. In the case of IL-1 beta + PDGF-BB the induction of PGE2 release was at least partly due to the synergistic induction of cyclooxygenase activity. These findings demonstrate that both proliferating and reversibly growth arrested HMCs release prostaglandins in response to various inflammatory stimulators and combinations thereof. The findings support the important role of HMC in the regulation of glomerular hemodynamics during inflammatory processes.
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PMID:Monokines and platelet-derived growth factor modulate prostanoid production in growth arrested, human mesangial cells. 210 53


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