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)

Two monocyte-derived cytokines, interleukin-1 (IL-1) and interleukin-6 (IL-6), have been reported to costimulate monocyte-depleted T cell populations in the presence of mitogen, and this effect has been attributed to an accessory function of these molecules. We have now examined further the accessory function potential of IL-1 plus IL-6, and examined how these cytokines promote T cell growth with mitogen. Together, IL-1 and IL-6 additively and, to a small degree, synergistically promote the proliferation of highly purified human peripheral blood T cells with phytohemagglutinin (PHA). However, maximum costimulation by IL-1 plus IL-6 over a wide range of concentrations is significantly smaller than that induced by optimal numbers of monocytes. Also, in contrast to monocytes that costimulate equally effectively T4 positive and T8 positive cells, IL-1 plus IL-6 costimulate T4 positive lymphocytes in marked preference to T8 positive cells. IL-1 plus IL-6 induces IL-2 secretion in T cell cultures costimulated with PHA, and an antibody to the IL-2 receptor, anti-Tac, markedly inhibits PHA-activated T cells costimulated by IL-1 plus IL-6. In addition, IL-1 plus IL-6 enhances the expression of surface IL-2 receptors. Because the costimulatory effect of IL-1 plus IL-6 is quantitatively smaller than that of monocytes, and it is preferentially directed toward T4 positive as opposed to T8 positive T cells, IL-1 plus IL-6, together, appear to represent a selective set of monocyte-derived accessory signals.
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PMID:Accessory function of interleukin-1 and interleukin-6: preferential costimulation of T4 positive lymphocytes. 196 55

Tumor-infiltrating lymphocytes (TIL) are a heterogeneous population of T cells with potent antitumor activity against a wide variety of tumors. TIL from renal cell cancer (RCC) typically exhibit diminished growth and antitumor activity after four weeks in vitro. We have therefore investigated effects of varying doses of interleukin-6 (IL-6) (0, 25, 100 units/ml.) on in vitro expansion, proliferation, cytotoxicity, and expression of cell surface phenotypes of long term renal TIL cultures from three RCC patients. Among the various conditions tested, three of three TIL cultures displayed a mild increase in cell expansion when grown in IL-2 with the addition of 100 units/ml. of IL-6. Two of three TIL cultures grown in IL-2 and 100 U/ml. of IL-6 demonstrated enhanced proliferation as determined by 3H-thymidine uptake. TIL could not be isolated or maintained in vitro when grown in the presence of IL-6 alone without IL-2. IL-6 was also found to enhance the long term non-specific cytotoxicity against an allogeneic nonrenal tumor target. No consistent effect on autologous tumor-specific cytotoxicity was demonstrated. We conclude that IL-6, when used in combination with IL-2, may modestly enhance the long-term growth of RCC-derived TIL.
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PMID:The effects of interleukin-6 on tumor-infiltrating lymphocytes derived from human renal cell cancer. 199 27

Current evidence suggests that the development of allosensitized cytotoxic T lymphocytes within sponge matrix allografts takes place primarily in situ and may be regulated by the secretory products of the cells infiltrating the graft. In vitro studies have implicated IL-2, IL-4, and IL-6 in CTL development. We have reported that TNF-alpha, macrophage colony-stimulating factor, IL-1, IFN-alpha, and IFN-beta are present in the allograft, but that IL-2 and IL-4 cannot be detected at any time using specific bioassays. In this study, we found significantly higher levels of IL-6 within the allografts compared with the syngeneic grafts. Peak IL-6 activity coincided with the appearance of allosensitized CTL in the allografts. IL-6 concentration in the serum of sponge allografted mice was less than 1% of that found in the graft. The sponge fluid exhibited both hybridoma growth factor and hepatocyte-stimulating factor activities in vitro, and both these activities were neutralized by antibody to murine IL-6 but not by antibody to murine IL-1-beta or TNF-alpha. Messenger RNA for murine IL-6 was detected in the graft-infiltrating cells. The high level of IL-6 found in the allograft coincident with the appearance of cellular immunity suggests that this cytokine might play some role in the development of allospecific CTL in vivo.
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PMID:Evidence that production of interleukin 6 within the rejecting allograft coincides with cytotoxic T lymphocyte development. 200 23

The effect of (n-3) fatty acid supplementation on cytokine production and lymphocyte proliferation was investigated in young (23-33 y) and older (51-68 y) women. Subjects supplemented their diets with 2.4 g of (n-3) fatty acid/d for 3 mo. Blood was collected before and after 1, 2 and 3 mo of supplementation. The (n-3) fatty acid supplementation reduced total interleukin (IL)-1 beta synthesis by 48% in young women but by 90% in older women; tumor necrosis factor was reduced by 58% in young and 70% in older women. Interleukin-6 was reduced in young women by 30% but by 60% in older women. Older women produced less IL-2 and had lower mitogenic responses to phytohemagglutinin (PHA) than young women prior to (n-3) fatty acid supplementation. The (n-3) fatty acid supplementation reduced IL-2 production in both groups; however, this reduction was significant only in older women. The PHA-stimulated mitogenic response was significantly reduced by (n-3) fatty acid in older women (36%). Thus, long-term (n-3) fatty acid supplementation reduced cytokine production in young women and cytokine production and T cell mitogenesis in older women. The reduction was more dramatic in older women than in young women. Although (n-3) fatty acid-induced reduction in cytokine production may have beneficial anti-inflammatory effects, its suppression of IL-2 production and lymphocyte proliferation in older women may not be desirable.
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PMID:Oral (n-3) fatty acid supplementation suppresses cytokine production and lymphocyte proliferation: comparison between young and older women. 200 7

The effect of recombinant human erythropoietin (Epo) on plasma cells was studied in a serum-free medium, COSMEDIUM-001 (Cosmedium). Epo enhanced both Ig production and thymidine uptake by human plasma cell lines, AF-10 and IM-9. Interleukin-6 (IL-6) enhanced both Ig production and thymidine uptake by AF-10 and IM-9, while other cytokines, including IL-1 beta, IL-2, IL-3, IL-4, IL-5, granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-alpha (IFN-alpha) or IFN-gamma, failed to do so. However, the Epo effect was specific since Epo-induced enhancement of Ig production and thymidine uptake was blocked by the anti-Epo antibody but not by the anti-IL-6 antibody or the control antibody. Conversely, IL-6-induced enhancement was blocked by the anti-IL-6 antibody but not by the anti-Epo antibody. Epo also enhanced Ig production (IgG, IgM, and IgA) and thymidine uptake by PCA-1+ plasma cells generated in vitro. This enhancement was also blocked by the anti-Epo antibody but not by the anti-IL-6 antibody. Taken together, these results suggest that Epo enhances plasma cell responses by a different mechanism than does IL-6.
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PMID:Erythropoietin enhances immunoglobulin production and proliferation by human plasma cells in a serum-free medium. 202 98

Compound IX 207-887 is a novel antiarthritic agent which inhibits the release of interleukin-1 (IL-1) from human monocytes and mouse peritoneal macrophages in vitro at concentrations which are achieved therapeutically in human rheumatoid arthritis and in animal models of arthritis. In the present studies IL-1 activity in conditioned media, homogenates or lysates was monitored using four independent assay systems. Biologically active IL-1 was determined by, a) the induction of latent metalloproteinase-release from rabbit articular chondrocytes, which is relatively specific for IL-1 and b) by a sensitive thymocyte proliferation assay. Immunoreactive IL-1-beta was assayed by RIA and ELISA. In all test systems IX 207-887 significantly reduced both biologically active and immunoreactive IL-1 in culture media, whereas the levels of IL-1 in homogenates or lysates were either unaffected or only marginally reduced. The release of other monokines tested, such as interleukin-6 and tumour necrosis factor-alpha, and the secretion of lysozyme were only marginally influenced. IX 207-887 neither affected the adherence of human monocytes nor markedly inhibited IL-1 or IL-2-induced thymocyte proliferation. In the chondrocyte test no IL-1 antagonistic activity of IX 207-887 could be observed. All of these data indicate that IX 207-887 has the novel property of being an inhibitor of IL-1 release.
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PMID:Inhibition of interleukin-1 release by IX 207-887. 238 8

A wide variety of cytokines have been demonstrated to affect B-cell function. However, it is unclear which of these mediators actually exert direct effects on the B cells themselves. In the present study, the direct role of interleukin (IL) 1, IL-2, Interferon-gamma, or Interferon-alpha in human B-cell activation, proliferation, or differentiation was examined and compared with the effects of a B-cell growth factor (BCGF) or a B-cell differentiation factor (BCDF). Highly purified human B lymphocytes were separated according to size into two nonoverlapping populations. The fraction of small B cells was incubated with IL-1, IL-2, Interferon-gamma, Interferon-alpha, BCGF, or BCDF, and cell size changes, RNA synthesis, DNA synthesis, or supernatant immunoglobulin (Ig) production were measured. Neither IL-1, IL-2, Interferon-alpha, Interferon-gamma, nor the BCGF induced substantial cell size changes, RNA synthesis, DNA synthesis, or Ig production by the small fraction of B lymphocytes; however, the BCDF could directly activate a proportion of resting B lymphocytes to secrete Ig. The fraction of large B cells was also incubated with these cytokines. While neither IL-1, Interferon-alpha, nor Interferon-gamma enhanced DNA synthesis or Ig production by the fraction of large B lymphocytes, DNA synthesis was augmented 23-fold by BCGF and IgG production was increased 7-fold by BCDF. Additionally, IL-2 slightly enhanced both proliferation and differentiation of large B cells but substantially less so than BCGF and BCDF; DNA synthesis was increased 4-fold, while Ig production in the presence of IL-2 was increased by approximately 50%. Thus, the most important lymphokines modulating the function of these two fractions of tonsillar lymphocytes were a BCGF and a BCDF.
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PMID:The direct effects of interleukin 1, interleukin 2, interferon-alpha, interferon-gamma, B-cell growth factor, and a B-cell differentiation factor on resting and activated human B cells. 242 21

After in vivo immunization with antigen, B cells appear in the peripheral blood which can be induced in vitro by nonspecific factors found in mixed lymphocyte culture supernatants (MLC-SN) to differentiate and secrete antibody specific for the immunizing antigen. In order to further delineate the nature of the factors involved in the differentiation of these in vivo-activated B cells, various helper factors, including interleukin 1 and interleukin 2 (IL-1 and IL-2), B-cell growth factor (BCGF), and B-cell differentiation factor (BCDF) were added separately and in combination to cultures of these preactivated B cells. T-cell-depleted fractions of peripheral blood mononuclear cells were obtained from normal individuals immunized in vivo with keyhole limpet hemocyanin. MLC-SN alone, without the addition of antigen, selectively triggered an antibody response specific for the antigen used to immunize in vivo in the absence of a polyclonal B-cell response. In order to obtain responses equal to those seen with MLC-SN, a combination of BCGF, IL-2, and BCDF was required, although any two factors partially reconstituted the response. Exogenous IL-1 had the least effect but was suppressive in the presence of optimal concentrations of monocytes. Thus, for maximal in vitro differentiation of in vivo-preactivated B cells, a combination of at least three helper factors is required and acts in a synergistic manner to induce antigen-specific antibody responses.
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PMID:Synergy of helper factors in the differentiation of in vivo-preactivated antigen-specific human B cells. 257 96

An assay system was developed to measure feline hybridoma growth factor (HGF)/interleukin-6 (IL-6) activity in biological samples containing many kinds of cytokines by using the proliferation of the newly established mouse-rat hybridoma clone, B3B1. The proliferative response of this B3B1 clone was IL-6-specific, and could not be promoted by other cytokines including IL-1, IL-2, IL-3, and granulocyte-colony-stimulating factor (G-CSF). The anti-human B-cell stimulatory factor 2 (BSF-2)/IL-6 antiserum did not neutralize feline HGF/IL-6 activity in conditioned media prepared from feline con A-stimulated splenocytes and unstimulated alveolar macrophages, indicating antigenic differences between species. Feline HGF/IL-6 was eluted into the fractions corresponding to a molecular weight of 30,000-40,000 in gel filtration, and into the fractions at a salt concentration of 0.2-0.3 M NaCl in anion exchange chromatography. The physicochemical properties of feline HGF/IL-6 were slightly different from those of murine and human IL-6.
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PMID:Feline hybridoma growth factor/interleukin-6 activity. 268 91

IL-6/IFN-beta 2 is a family of phosphoglycoproteins ranging in size from 19 to 30 kDa which elicits a broad range of physiologic and immune responses. Several cytokines, including TNF, have been shown to stimulate IL-6 production in cell culture. In this report, we describe the rapid induction of circulating biologically active IL-6 by the systemic administration of rTNF to patients with cancer. Low levels of IL-6 activity could be detected in the sera of patients as early as 5 min after rTNF infusion. IL-6 levels peaked approximately 2 to 3 h after rTNF bolus administration and were undetectable in most cases within 8 h. IL-6 was detected in two separate bioassays--the hybridoma B9 proliferation and the hepatocyte-stimulating factor assay. Maximum detectable levels of IL-6 ranged from 160 to 310 hybridoma growth factor units and 11-82 ng/ml in the hepatocyte-stimulating factor assay. IL-6 induction decreased after serial, daily doses of rTNF. Serial serum samples of patients receiving IL-2 or IFN-alpha were also assayed for IL-6 production. IL-2-treated but not IFN-alpha-treated patients generated low levels of IL-6 (range less than 20 to 95 hybridoma growth factor units/ml). Interestingly, in patients treated with IL-2, serum levels of TNF were detectable and peak TNF activity preceded measurable IL-6 levels. Serum levels of acute phase plasma proteins and of corticosteroid rose in response to rTNF administration. C-reactive protein increased (2.5 to 4.0-fold) within 8 h of rTNF administration and cortisol levels rose (10- to 20-fold) within 4 h after rTNF injection. We conclude that rTNF administration in man leads to the induction of circulating IL-6 which, due to its broad range of activities, may be an important physiologic signal regulating the immune response.
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PMID:IL-6/IFN-beta-2 as a circulating hormone. Induction by cytokine administration in humans. 278 45


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