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)

Recombinant growth factors and proinflammatory cytokines were added to primary cultures of human intrahepatic biliary duct epithelia to test for their ability to stimulate DNA synthesis and elicit cytokine production. Interleukin-6 and hepatocyte and epidermal growth factors were found to increase the DNA labeling index of biliary duct epithelium from fourfold to sixfold 24 hr after their addition to primary biliary duct epithelium cultures maintained in serum-free medium. The proliferative responses to all three biliary duct epithelium mitogens peaked within 24 hr, and hepatocyte growth factor was effective over a concentration range of 1.0 to 50 ng/ml, whereas interleukin-6 was effective from 1 to 1,000 U/ml. Insulin-like growth factor, phorbol myristate acetate, interleukin-1 beta and platelet-derived growth factor BB showed mild stimulatory effects, whereas interleukin-4, gamma-interferon, phytohemagglutinin and platelet-derived growth factors AA and AB did not increase DNA synthesis in biliary duct epithelium. Interleukin-1 beta and phorbol myristate acetate were also shown to induce in a dose-dependent fashion a threefold to fivefold increase of interleukin-6 production as measured by enzyme-linked immunosorbent assay in human primary biliary duct epithelium cultures, when compared with hepatocyte growth factor, epidermal growth factor, insulin-like growth factor, phytohemagglutinin, tumor necrosis factor-alpha or platelet-derived growth factor. These results show that interleukin-6 participates in growth regulation of human biliary duct epithelium. This could be exerted in a paracrine or autocrine manner.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Human biliary epithelial cells secrete and respond to cytokines and hepatocyte growth factors in vitro: interleukin-6, hepatocyte growth factor and epidermal growth factor promote DNA synthesis in vitro. 804 98

As vitamin E enhances immune responses, it may reduce dietary ethanol (EtOH)-induced immune suppression, thereby favorably affecting host disease resistance. The effects of dietary vitamin E at higher level in alcohol-fed female C57BL/6 mice was determined via in vitro cytokine production by splenocytes and thymocytes, and some other immune functions. A 15-fold increase of vitamin E (160 IU/liter) in a liquid diet (National Council Research), with or without EtOH (4.5%, v/v), was fed to mice for 10 weeks. Vitamin E supplementation restored production of interleukin-2, -5, -6, -10, and interferon-gamma by concanavalin A (Con A)-stimulated splenocytes and interleukin-6 and tumor necrosis factor-alpha by lipopolysaccharide-stimulated splenocytes, which were suppressed by dietary EtOH. However, it had no effect on interleukin-4 secretion, which was also reduced by splenocytes from EtOH-fed mice. Vitamin E supplementation also restored EtOH-suppressed, mitogen-induced splenocyte proliferation, but not thymocyte proliferation, although it slightly increased production of immunoglobulin A and G by lipopolysaccharide-stimulated splenocytes, which were suppressed by dietary EtOH. Dietary vitamin E, furthermore, significantly increased interleukin-2 and -6 secretion by Con A-stimulated thymocytes, which were suppressed by dietary EtOH, although it had no effect on interleukin-4 and interferon-gamma production by Con A-stimulated thymocytes from EtOH-fed mice. These data suggest that dietary vitamin E supplementation can modulate dysregulation of cytokines initiated by dietary EtOH and restore immune dysfunctions induced by EtOH ingestion.
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PMID:Dietary vitamin E modulation of cytokine production by splenocytes and thymocytes from alcohol-fed mice. 804 38

Cellular turnover of the hematopoietic system is supported by a small population of cells termed hematopoietic stem cells. Stem cells are capable of self-renewal and differentiation into individual lymphomyeloid lineages. Available evidence indicates that the decision of a stem cell to self-renew or differentiate and the decision of a multipotential progenitor to select a lineage pathway during differentiation (commitment) are intrinsic to the progenitors and are stochastic in nature. In contrast, proliferative kinetics of the progenitors, namely, survival and expansion of the progenitors, appear to be controlled by a number of interacting cytokines. Whereas proliferation and maturation of committed progenitors are controlled by late-acting factors such as erythropoietin, macrophage colony-stimulating factor, granulocyte colony-stimulating factor, and interleukin-5, progenitors at earlier stages of development are controlled by a group of several overlapping cytokines. Interleukin-3, granulocyte/macrophage colony-stimulating factor, and interleukin-4 regulate proliferation of multipotential progenitors only after they are triggered to exit from dormancy state. Triggering of cycling of dormant primitive progenitors and proliferation of lymphohemopoietic primitive progenitors appear to require interactions of early acting cytokines including interleukin-6, granulocyte colony-stimulating factor, interleukin-11, interleukin-12, leukemia inhibitory factor, and steel factor.
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PMID:Hematopoiesis. 808 74

We have studied, in 10 patients undergoing hip replacement surgery, the release of cytokines (tumour necrosis factor-alpha (TNF-alpha), interleukin-1 alpha (IL-alpha), interleukin-1 beta (IL-1 beta), interleukin-4 (IL-4), interleukin-6 (IL-6) and interleukin-8 (IL-8)) in association with retransfusion of autologous shed blood. The patients were reinfused with whole blood collected after operation. The median volume returned to the patients was 300 ml whole blood (25-75% range = 300-425 ml). Before reinfusion, blood was filtered. Plasma concentrations of IL-6 increased 1 and 60 min after retransfusion (P < 0.05). The plasma concentrations of TNF-alpha, IL-1 alpha, IL-1 beta, IL-4 and IL-8 did not change significantly after retransfusion of shed wound blood. However, there were increased concentrations of IL-1 alpha, IL-1 beta, IL-6 and IL-8 in the collected blood (P < 0.001). The filtration procedure did not reduce significantly the concentrations of these factors. This study shows that whole blood collected from a surgical wound contains large concentrations of cytokines. Filtration of the shed wound blood did not reduce significantly these levels and retransfusion caused increased plasma concentrations of IL-6.
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PMID:Formation of cytokines by retransfusion of shed whole blood. 815 44

To explore the pathogenic mechanisms involved in adenovirus infection, we evaluated total levels of immunoglobulins, antiadenovirus antibodies, adenovirus-specific circulating immune complexes, and cytokines in serum samples obtained from 38 hospitalized children with adenovirus infection. According to their clinical findings and outcome, the infections were classified as follows: (1) moderate (group I, n = 10), (2) severe (group II, n = 12), and (3) fatal (group III, n = 16). About 60% of the children had elevated IgM levels. IgG-containing adenovirus-specific circulating immune complexes were initially detected in 7 of 16 group III patients, 4 of whom had low serum levels of the third component of complement. A decrease in initial antiadenovirus IgG antibodies was observed in 3 of 10 patients in group III. Serum interleukin-6 was not detected in group I (none of 10), but was present in group II (7 of 12, p = 0.016) and group III (13 of 16, p < 0.001). Interleukin-8 was detected in all groups; values in fatal cases were significantly higher than in surviving children. Tumor necrosis factor alpha was not observed in group I (none of 10) and was uncommon in group II (2 of 12) but was frequently detected in group III (9 of 15, p = 0.01). Interleukin-1 and interleukin-4 were rarely detected in serum samples. Increased concentrations of interleukin-6, interleukin-8, and tumor necrosis factor alpha were associated with hypoperfusion, febrile peaks, tonic-clonic seizures, and septic shock. In 5 of 10 patients in groups II and III, autoantibodies specific for smooth muscle were found. Our findings indicate that high serum values for interleukin-6, interleukin-8, and tumor necrosis factor alpha are associated with severity of adenovirus infection.
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PMID:Cytokines in adenoviral disease in children: association of interleukin-6, interleukin-8, and tumor necrosis factor alpha levels with clinical outcome. 817 57

Cytokines are thought to cause the depression of cytochrome P-450 (CYP)-associated drug metabolism in humans during inflammation and infection. We have examined the role of five cytokines, i.e., interleukin-1 beta, interleukin-4, interleukin-6, tumor necrosis factor-alpha, and interferon-gamma, on the expression of CYP1A2, CYP2C, CYP2E1, CYP3A, and epoxide hydrolase in primary human hepatocyte cultures. Steady state P-450 and epoxide hydrolase mRNA levels, as well as ethoxyresorufin-O-deethylase and nifedipine oxidation activities, which are mainly supported by CYP1A1/1A2 and CYP3A, respectively, were measured. Interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha were found to be the most potent depressors of P-450 enzymes. After 3 days of treatment, both mRNA levels and enzyme activities were depressed, typically by at least 40%, whatever the cytokine and the enzyme considered. Interferon-gamma also suppressed CYP1A2 and CYP2E1 mRNA levels and ethoxyresorufin-O-deethylase activity but had no effect on CYP3A and epoxide hydrolase mRNAs. In addition, interleukin-4 had the opposite effect, compared with other cytokines, on CYP2E1 mRNA, which was increased up to 5-fold; ethoxyresorufin-O-deethylase and nifedipine oxidation activities were not significantly affected. These results provide the first demonstration that various cytokines act directly on human hepatocytes to affect expression of major P-450 genes and that a wide range of responses can be observed among the enzymes for a given cytokine, suggesting that different regulatory mechanisms may be involved.
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PMID:Cytokines down-regulate expression of major cytochrome P-450 enzymes in adult human hepatocytes in primary culture. 823 20

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

Previous studies have shown that interleukin-4 (IL-4) may have both stimulatory and inhibitory effects on the growth of normal and malignant B-cells in vitro. We studied the effects of IL-4 on tumour necrosis factor (TNF) induced and spontaneous proliferation (3H-TdR incorporation) and spontaneous release of TNF and interleukin-6 (IL-6) by purified B-cell chronic lymphocytic leukaemia (CLL) cells in vitro. TNF (100 U/ml) increased 3H-TdR uptake in cells to 700 +/- 302% of control (mean +/- S.E., n = 9, p = 0.033). Recombinant IL-4 (10 ng/ml) consistently inhibited DNA synthesis in all CLL patients studied. When added at the start of 5 day cultures, IL-4 inhibited both spontaneous (41 +/- 17% inhibition, n = 3) and TNF induced (46 +/- 5% inhibition, n = 9, p = 0.01) 3H-TdR uptake. Similar results were obtained when IL-4 was added after 48 h of culture. This effect of IL-4 was dose dependent. Inhibition was not related to clinical stage. IL-4 (whether added at T0 or T48h) also inhibited spontaneous release of TNF and IL-6 measured at 48 and 120 h. TNF and IL-4 had no consistent effect on normal cord blood CD5+ B-cells. These data show that IL-4 has inhibitory effects on B-CLL DNA synthesis and also inhibits spontaneous release of IL-6 and TNF in vitro. IL-4 may have a role in vivo in reducing proliferation in these B-cell malignancies by inhibiting potential autocrine growth loops.
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PMID:Interleukin-4 (IL-4) inhibits proliferation and spontaneous cytokine release by chronic lymphocytic leukaemia cells. 828 67

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

Interleukin-4 (IL-4) modulates the activity of a variety of lymphoid, hemopoietic and mesenchymal cells, but little is known about its influence on bone cells. We have studied the effects of IL-4 on the human osteoblast-like cell line MG63. IL-4 (0.1-50 ng/ml) inhibited cell proliferation. The effect did not depend on cell density, but it was more marked in serum-free cultures than in the presence of serum. IL-4 also induced a dose-dependent increase in the expression of alkaline phosphatase stimulated by 1,25-dihydroxyvitamin D3, a marker of differentiated osteoblast activity. However, IL-4 did not modify the secretion of interleukin-6 or tumor necrosis factor. These results suggest that interleukin-4 may play a role as a modulator of osteoblast activity.
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PMID:Effects of interleukin-4 on human osteoblast-like cells. 832 20


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