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)

Expression of four cytokine genes, transforming growth factor (TGF) beta 2, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and macrophage colony-stimulating factor (CSF-1 also known as M-CSF) was examined to determine whether these genes are developmentally regulated in the brain. Northern blots were performed on RNA isolated from the mouse brain from embryonic day 15 (E15) through postnatal day 9. TGF beta 2 gene expression was relatively high in the earliest embryos studied and decreased after E16-E17, and the three transcripts were developmentally regulated. TNF-alpha and IL-6 were detected in total RNA on all days studied. CSF-1 was detected only in polyadenylated RNA. The data suggest that expression of these cytokines is related to specific developmental events that share cellular functions with regenerative or inflammatory processes.
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PMID:Developmental regulation of cytokine expression in the mouse brain. 814 54

Stimulation of human peripheral blood monocytes with the thyroid hormones tri-iodothyronine (T3) and thyroxine (T4) enhanced their ability to mature into cytologically and functionally characteristic veiled/dendritic cells. Veiled/dendritic cell transition induced by T3 and T4 was dependent on the production of granulocyte-macrophage colony-stimulating factor (GM-CSF), tumour necrosis factor-alpha (TNF alpha) and interleukin-6 (IL-6) in the culture, since the addition of antibodies specific for GM-CSF, TNF alpha and IL-6 to the culture system had blocking effects. The addition of antibodies to macrophage colony-stimulating factor and IL-1 had no effects. Contaminating T cells and B cells did not contribute to the transition of monocytes to veiled/dendritic cells, and it is therefore likely that the GM-CSF, TNF alpha and IL-6 produced in the culture system were derived from the monocytes themselves. Stimulation of the blood monocytes with an optimal concentration of metrizamide (14.5%), reverse T3 (rT3; 2 x 10(-10) M) or highly iodinated thyroglobulin (Tg; 2 x 10(-11) M) also resulted in an increased transition of monocytes to veiled/dendritic cells, but to a lesser extent in comparison with the thyroid hormones (T3, 31 +/- 6% and T4, 25 +/- 5% vs rT3, 22 +/- 8% and Tg with an iodination grade of 0.37%: 20 +/- 4% veiled/dendritic cells). Administration of anti-GM-CSF, anti-TNF alpha and anti-IL-6 to the culture system also had blocking effects on the transition from monocytes to veiled/dendritic cells induced by the iodinated compounds. The mechanisms by which such iodinated compounds act on the monocyte to veiled/dendritic cell transition can only be speculated on (interference H2O2-generating system?).
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PMID:Effect of thyroid hormones and other iodinated compounds on the transition of monocytes into veiled/dendritic cells: role of granulocyte-macrophage colony-stimulating factor, tumour-necrosis factor-alpha and interleukin-6. 818 78

Chronic ethanol ingestion predisposes to tuberculosis and bacterial pneumonia. Mycobacterium avium complex organisms cause bacteremia in patients with AIDS. Human macrophages and murine Kupffer cells exposed to ethanol are more permissive towards intracellular growth of M. avium than control mononuclear phagocytes. Ethanol also has been shown to impair the ability of human macrophages and murine Kupffer cells to respond to stimulation with tumor necrosis factor (TNF) and granulocyte macrophage colony stimulating factor (GM-CSF), and to produce cytokines such as interleukin-1, interleukin-6, and TNF when properly stimulated. The impairment is dependent in part on a downregulation in the number of TNF receptors on the macrophage's membrane. Recent evidence suggests that ethanol in nonlethal concentrations induces stress-related proteins in M. avium, leading to the inhibition of intracellular pathways in the macrophage and, consequently, impairing some of its functions. In summary, ethanol acts both on the host and on the mycobacterium in a complex sequence of events that influence the outcome of the infection.
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PMID:Effect of ethanol on the interaction between the macrophage and Mycobacterium avium. 820 5

The objective of this phase-I study was to establish the maximum tolerable dose of recombinant human interleukin-3 (rhIL-3) after salvage chemotherapy in patients with malignant lymphoma. Twenty-one patients with relapsed Hodgkin's disease or intermediate/high-grade non-Hodgkin's lymphoma received rhIL-3 after the second cycle of DHAP chemotherapy (cisplatin, cytosine-arabinoside, dexamethasone). Cycles 1 and 3 were given without rhIL-3. The rhIL-3 was administered as a continuous intravenous infusion for 10 days starting 48 h after chemotherapy in cycle 2. Five different dose levels of rhIL-3 (0.25, 1.0, 2.5, 5.0, and 10.0 micrograms/kg/day) were sequentially tested. At the three lowest dose levels one double-blinded placebo was included for every four patients per dose level. Low-grade fever occurred in 15/21 patients, unrelated to the dose of rhIL-3. Nausea and vomiting (grade 1-2) occurred in seven patients. Headache was dose related, with 3/4 patients at a dose of 10 micrograms/kg/day experiencing troublesome grade-2 headache precluding further dose escalation. Facial flushing developed in 3/8 patients at the highest dose levels of rhIL-3. There was a significant increase in eosinophil count during rhIL-3 (p = 0.03 cycle 2 vs cycle 1 and p = 0.002 cycle 2 vs cycle 3) without accompanying clinical signs of symptoms. No increase in basophil count was observed. There were no increased plasma levels of interleukin-6 or macrophage colony-stimulating factor (M-CSF) during rhIL-3. We conclude that rhIL-3 can be safely administered as a continuous intravenous infusion for 10 days after DHAP chemotherapy. Dose-limiting side effects, especially headache, occur at a dose of 10 micrograms/kg/day.
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PMID:The tolerability of continuous intravenous infusion of interleukin-3 after DHAP chemotherapy in patients with relapsed malignant lymphoma. A phase-I study. 821 38

The process of bone remodeling involves complex interactions between the osteoclast, the primary bone-resorbing cell, and other cells in its microenvironment. These interactions can regulate bone resorption through two processes: (1) effects on the number of osteoclasts present at a given site and (2) effects on the bone-resorbing capacity of individual osteoclasts. Cells present in the osteoclast microenvironment include marrow stromal cells, osteoblasts, macrophages, T-lymphocytes, and marrow cells. These cells, as well as the osteoclast itself, produce cytokines that can affect osteoclast formation and osteoclast activity. In vitro model systems using rodent organ cultures or long-term marrow culture systems, and in vivo models have demonstrated that cytokines such as interleukin-1, M-CSF, tumor necrosis factor, and interleukin-6 can stimulate the formation and bone-resorbing capacity of osteoclasts. In contrast, cytokines such as interleukin-4, gamma-interferon, and transforming factor-beta inhibit both osteoclast formation and osteoclast activity. The relative proportions of these cytokines in the marrow microenvironment may play a critical role in regulating osteoclast activity. Knowledge of cytokines that affect osteoclast formation and activity and their capacity to modulate the bone-resorbing process should provide critical insights into normal calcium homeostasis and disorders of bone turnover such as osteoporosis and Paget's disease of bone.
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PMID:Role of cytokines in the regulation of bone resorption. 827 87

It is often assumed that macrophage-colony stimulating factor (M-CSF) or CSF-1, as well as granulocyte macrophage-CSF (GM-CSF), can induce inflammatory mediator production by monocytes/macrophages. We demonstrate with elutriation-purified human monocytes that, in contrast to lipopolysaccharide, recombinant human CSF-1 does not induce secretion of prostaglandin E2, interleukin-6 (IL-6), IL-1 beta, or tumor necrosis factor alpha, as measured by immunoassay; however, increased urokinase-type plasminogen activator (u-PA) activity in cell lysates and mRNA was observed. Similar results were obtained when the monocytes were treated with recombinant human GM-CSF. Such increased u-PA expression may contribute to the function of CSF-1 at sites of inflammation.
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PMID:Effects of macrophage-colony stimulating factor on human monocytes: induction of expression of urokinase-type plasminogen activator, but not of secreted prostaglandin E2, interleukin-6, interleukin-1, or tumor necrosis factor-alpha. 831 54

Endothelial cells (EC) may regulate both local and systemic aspects of inflammation through the synthesis of cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), macrophage colony-stimulating factor (M-CSF), and interleukin-6 (IL-6). EC are known to synthesize these cytokines in response to interleukin-1 (IL-1 alpha), tumor necrosis factor-alpha (TNF-alpha) and lipopolysaccharide (LPS). In this paper, we illustrate the effect of interleukin-4 (IL-4) in reducing the synthesis of GM-CSF by EC stimulated with IL-1 alpha, TNF-alpha, or LPS. This is compared with the previously reported strong synergy between IL-4 and IL-1 alpha, TNF-alpha, or LPS in the synthesis of IL-6 by EC. No clear effect of IL-4 was seen in the synthesis of G-CSF or M-CSF. The range of concentrations of IL-4 at which these effects were seen was identical for both reduced GM-CSF synthesis and increased IL-6 synthesis. The effect of IL-4 on IL-6 synthesis was seen by 4 h of treatment, while that on GM-CSF was apparent between 4 and 8 h. It is suggested that these contrasting effects of IL-4 may reflect a biological role for this cytokine in the regulation of leukocytosis and the acute phase response.
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PMID:Contrasting effects of interleukin-4 on colony-stimulating factor and interleukin-6 synthesis by vascular endothelial cells. 832 81

Secretion of different cytokines may be an important T-cell effector mechanism for bone marrow engraftment, graft versus host disease and graft versus leukaemia effects after allogeneic bone marrow transplantation (BMT). Cytokine secretion and autocrine proliferative capacity of T-cell clones derived from leukaemia patients 3-6 weeks after allogeneic bone marrow transplantation were investigated. Only a minority of post-transplant T-cell clones (23/120; 19%) was capable of undergoing autocrine proliferation. By contrast, 21/65 (32%) normal control clones from the marrow donors derived under the same conditions were autocrine proliferative. All clones were interleukin-2 (IL-2) responsive. A majority (12/17; 71%) of autocrine proliferating post-transplant clones secreted detectable IL-2. Compared with control clones, CD4+ T-cell clones derived early after BMT produced decreased levels of interleukin-4 (IL-4) and interleukin-6 (IL-6), whereas secretion of interleukin-3 (IL-3) and granulocyte/macrophage colony-stimulating factor (GM-CSF) showed no significant difference. The small number (n = 8) of posttransplant CD8+ clones showed decreased production of IL-3, IL-4 and IL-6 compared with control clones, but normal secretion of GM-CSF. Neither CD4+ nor CD8+ T-cell clones secreted interleukin-7 (IL-7).
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PMID:Secretion of IL-2, IL-3, IL-4, IL-6 and GM-CSF by CD4+ and CD8+ TCR alpha beta+ T-cell clones derived early after allogeneic bone marrow transplantation. 832 61

After differentiation either with exogenous macrophage (M) or with granulocyte/macrophage (GM) colony-stimulating factor (CSF) microglial cells were isolated from neonatal mouse brain cell cultures and were comparatively tested for secretory immune effector cell functions. Both factors obviously do not promote the development of cells with biased growth requirement; however, the two microglia populations displayed distinct potentials to produce inflammatory cytokines. Upon gradual stimulation by lipopolysaccharide, the cells harvested from M-CSF-driven culture released more interleukin-1 and tumor necrosis factor activity, GM-CSF-grown cells on the contrary proved superior in interleukin-6 secretion. This pattern was paralleled by corresponding different kinetics of cytokine release in both types of microglial cells. When infected with Toxoplasma gondii only GM-CSF-differentiated cells were able to restrict the intracellular multiplication of tachyzoites in the absence of external stimuli. As described for interferon-gamma-treated macrophages, the antiparasitic activity of this microglia population is due to the synthesis of reactive nitrogen intermediates, since it was antagonized by NG-monomethyl-L-arginine, a competitive inhibitor of the arginine-dependent metabolic pathway. Complementary to previous data which attest an intrinsic capability for antigen presentation to GM-CSF-grown microglia, the functional state of the cells elicited by M-CSF and GM-CSF, respectively, may correspond to the resting and an activated form of microglia as distinguished in vivo.
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PMID:Functional dichotomy of mouse microglia developed in vitro: differential effects of macrophage and granulocyte/macrophage colony-stimulating factor on cytokine secretion and antitoxoplasmic activity. 833 Nov 61

Fibroblasts of the pulmonary interstitium are intimately involved in the response of the lung to inflammation as well as in repair of injured tissues. The response of fibroblasts within an inflammatory site appears to be directed, in part, by peptide mediators. Neutral endopeptidase (NEP), a metallopeptidase on the surface membrane of fibroblasts, can inactivate various vasoactive peptides, including kinins and tachykinins. Because lung fibroblasts both secrete cytokines and respond to mediators within the immediate environment, NEP might be regulated by locally generated cytokines. We found that several cytokines, including interleukin-1 alpha (IL-1), tumor necrosis factor-alpha (TNF-alpha), transforming growth factor, interleukin-6, and granulocyte macrophage colony-stimulating factor, enhanced activity of NEP on the surface of intact fibroblasts. In contrast, cultured pleural mesothelial cells had much lower levels of NEP than fibroblasts, and the enzyme was not enhanced by either IL-1 or TNF-alpha. Further studies with IL-1 showed that the effect required at least 6 h of exposure to the cytokine and depended upon final cytokine concentration. Combinations of IL-1 with other cytokines increased NEP activity beyond that in cells treated with individual cytokines, but combinations had less than additive effects. Selected pharmacologic agents indicated that the mechanism involves second messenger pathways. The cytokine effect on NEP was attenuated by indomethacin, an inhibitor of cyclooxygenase, by N-[2-(methylamino) ethyl]-5-isoquinolinesulfonamide dihydrochloride, an inhibitor of protein kinase, and by adenosine 3',5' cyclic monophosphothionate, an analog of cyclic adenosine monophosphate (cAMP) that competitively inhibits the cAMP signal pathway. It was mimicked by dibutyryl cAMP and by forskolin, an activator of adenyl cyclase.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cytokines increase neutral endopeptidase activity in lung fibroblasts. 838 Feb 49


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