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)

The treatment of keloids in black patients remains a medical dilemma. Previous studies have focused on primary alterations in the metabolism of fibroblasts as the key in the etiology of this condition. Yet alterations in the production of various cytokines which may alter fibroblast responses secondarily have received little attention. Twelve black patients with clinical and histological diagnosis of keloids and eight black control volunteers were studied. Peripheral blood mononuclear-cell (PBMC) fractions from both groups were assayed for production of interleukin-1 (IL-1), interleukin-2 (IL-2), interleukin-6 (IL-6), alpha-interferon (IFN-alpha), beta-interferon (IFN-beta), gamma-interferon (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and tumor necrosis factor-beta (TNF-beta). The production of IFN-alpha, IFN-gamma, and TNF-beta were markedly depressed in keloid patients compared to normal controls. However, IL-1 and IL-2 production was not significantly different between the two groups. In contradistinction, keloid patients produce greater amounts of IL-6, TNF-alpha, and IFN-beta. Altered levels of immunoregulatory cytokines may play a significant role in the net increase in collagen which characterizes keloid formation.
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PMID:Altered cytokine production in black patients with keloids. 151 3

Our results indicate that ST 789 exhibits complex immunomodulant properties. In fact, we found that ST 789 inhibits the expression of activation antigens, such as interleukin-2 and transferrin receptors by peripheral blood mononuclear cells (PBMCs) from healthy subjects following mitogen stimulation, but we were not able to detect under the same experimental conditions any effect on the in vitro production of soluble CD8 antigen and of interleukin-4 as well as on the proliferative response of antigen-specific and autoreactive human T cell lines. Finally, we showed that ST 789 is able to strongly enhance the in vitro production of interleukin-6 by PHA-stimulated PBMCs. The reduced expression of activation antigens in the presence of ST 789 does not seem to be mediated by CD8+ suppressor T lymphocytes, as indicated by the normal soluble CD8 levels in culture media, but rather reflects a direct inhibitory action on T helper proliferation and likely on interleukin-2 secretion. The strong enhancement by ST 789 of the in vitro interleukin-6 production seems to indicate the most relevant possibility of clinical applications in human diseases.
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PMID:Modulation by ST 789 of in vitro lymphocyte activation and cytokine production. 158 23

Multiple myeloma remains a fatal disease. However, in the last few months new biologic and clinical information has been provided about this disease. In particular, the immunophenotype of myeloma cells seems to indicate, at least in some patients, the possibility of a stem cell involvement in the pathogenesis of myeloma. Moreover, the recent progress in understanding the complex cytokine network has revealed the possibility that myelomatous proliferation is highly influenced by some cytokines such as interleukin-6, interleukin-3, interleukin-2, and granulocyte-macrophage colony-stimulating factor. Furthermore, it has been shown that the mechanism responsible for the resistance of myeloma cells to chemotherapy may be partially overcome by the use of calcium antagonists associated with quinine. Finally, new insights into the pathogenesis and biology of the disease have been provided by studies of molecular biology and flow cytometry undertaken in multiple myeloma patients. The best conventional induction treatment remains to be defined. However, the increased use, as new therapeutic modalities, of interferon-alpha and transplantation procedures in multiple myeloma opens new hopes of a cure. In the future, a better comprehension of the multiple myeloma biology associated with a wider use of new and more effective therapeutic approaches will certainly improve the natural course of the disease.
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PMID:Biology and treatment of multiple myeloma. 159 Dec 96

Glucocorticoid hormones, calcium ionophores and anti-CD3 monoclonal antibodies induce apoptosis in mouse thymocytes. This type of cell death, which is characterized by an extensive DNA fragmentation into oligonucleosomal subunits, occurs in the intrathymic process of negative selection, and is involved in the deletion of autoreactive T-cells during thymic maturation. A number of cytokines are able to modulate apoptosis, and interleukins, including interleukin-1, interleukin-2, and interleukin-4, play a crucial role in thymic maturation and T-cell development. We tested the effects of several cytokines on the glucocorticoid hormone-induced apoptosis of mouse thymocytes in vitro, and demonstrated that interleukin-1 alpha, interleukin-2, and interleukin-4 inhibit the apoptosis induced by dexamethasone, but that interleukin-3 and interleukin-6 exert no noteworthy effect. Dose-response experiments indicated that interleukin-4 is more potent than interleukin-1 alpha and interleukin-2 in inhibiting dexamethasone-induced apoptosis. Furthermore, interleukin-4 fully inhibited the DNA fragmentation induced by the protein kinase-C activator 12-O-tetradecanoylphorbol-13-acetate, but was ineffective against apoptosis induced by the calcium ionophore A23187. These results suggest that interleukins regulate the thymic selection process by acting as modulators of the negative selection process.
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PMID:Interleukins modulate glucocorticoid-induced thymocyte apoptosis. 159 84

This study was designed to examine cytokine production in a group of 22 well-trained runners covering a distance of 20 km within 2 hr. After running, all participants displayed a marked granulocytosis for 7 hr. Plasma neopterin levels increased 1 hr after exercise for 24 hr. Except for interleukin-6 (IL-6), cytokines were not reliably detected in plasma but were present in urine. Already before exercise, cytokines were detected in the urine of runners when compared to sedentary controls. Directly after running, interferon-gamma and tumor necrosis factor-alpha were further elevated but rapidly declined to preexercise levels. Interleukin-1 beta and interleukin-6 increased at a slower rate after exercise but secretion into urine persisted longer until 12 and 7 hr, respectively. Interleukin-2 (IL-2) was not detected but soluble IL-2 receptors appeared in the urine directly after running. Enhanced cytokine levels were accompanied by an only low creatinin kinase increase, indicating little muscle damage. These data show that long-distance running elevates cytokine production which supports the concept that regular, but not excessive, physical exercise may be beneficial by maintaining a stimulated immune system.
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PMID:Enhanced release of cytokines, interleukin-2 receptors, and neopterin after long-distance running. 161 21

The direct effects of pro-inflammatory cytokines on the contractility of mammalian heart were studied. Tumor necrosis factor alpha, interleukin-6, and interleukin-2 inhibited contractility of isolated hamster papillary muscles in a concentration-dependent, reversible manner. The nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) blocked these negative inotropic effects. L-Arginine reversed the inhibition by L-NMMA. Removal of the endocardial endothelium did not alter these responses. These findings demonstrate that the direct negative inotropic effect of cytokines is mediated through a myocardial nitric oxide synthase. The regulation of pro-inflammatory cytokines and myocardial nitric oxide synthase may provide new therapeutic strategies for the treatment of cardiac disease.
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PMID:Negative inotropic effects of cytokines on the heart mediated by nitric oxide. 163 60

Ursodeoxycholic acid was recently recognized as an effective agent in the treatment of primary biliary cirrhosis. Experimental evidence supporting the usefulness of ursodeoxycholic acid as a potentially beneficial therapeutic agent for primary biliary cirrhosis has been reported from the biochemical and physiological aspects. In this study, we investigated the direct effects of ursodeoxycholic acid on immunoglobulin and cytokine production in vitro using plaque-forming cell assay and enzyme-linked immunosorbent assay. It was demonstrated that ursodeoxycholic acid suppressed the production of IgM, IgG and IgA induced by Staphylococcus aureus Cowan I in peripheral blood mononuclear cells derived from healthy subjects and patients with primary biliary cirrhosis and also in human B lymphoma cell lines. Furthermore, ursodeoxycholic acid suppressed interleukin-2 and interleukin-4 production induced by concanavalin A and interferon-gamma production induced by polyinosinic-polycytidylic acid, but it did not affect interleukin-1 and interleukin-6 production induced by lipopolysaccharide in peripheral blood mononuclear cells. In addition, ursodeoxycholic acid suppressed the concanavalin A-induced thymocyte proliferation mediated by interleukin-1. Cytotoxicity against lymphocytes was not observed at the concentrations of ursodeoxycholic acid used. These results suggest that the beneficial effect of ursodeoxycholic acid in primary biliary cirrhosis is mediated in part by immunosuppression.
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PMID:Immunomodulatory effects of ursodeoxycholic acid on immune responses. 163 44

Plasma levels of interleukins 1, 2, 4 and 6 and tumor necrosis factor (TNF) were measured from 0 to 30 days in rats after a unilateral crush of the sciatic nerve at the level of the sciatic notch and after sham operations without nerve crush. Interleukin-6 was observed to peak and return to baseline levels within 24 h and remained at baseline for the duration of the experiment. An initial sharp rise in interleukin-1 and TNF was observed in all animals 1-2 days after the operation. A transient increase in interleukin-1 and TNF was also observed only in nerve-injured animals between 10 and 14 days after injury. A large increase in interleukin-2 appeared only in nerve-injured animals beginning at 11 days after injury and remained elevated for the remaining study period. No alterations in plasma interleukin-4 were observed at any time point. The experiments provide preliminary evidence for significant trauma-induced alterations in plasma cytokines which could provide a basis for some of the diffuse responses of peripheral neurons to trauma. The biphasic nature changes in plasma cytokines suggest that the immune system may participate in tissue reactions involved in the recovery from nerve injury.
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PMID:Changes in plasma cytokines associated with peripheral nerve injury. 164 99

Transferrin receptor expression is vital for the continuous growth of most cells. Although iron plays a key role in modulating transferrin receptor expression, other physiological factors are also capable of affecting receptor expression. In hematopoietic cells, these include interleukin-2, interleukin-6, calcium channels, cyclic nucleotides, phorbol esters and viruses. In this review, we will describe how these agents can alter transferrin receptor expression at the levels of transcription, translation and receptor re-cycling.
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PMID:Regulation of transferrin receptor expression and control of cell growth. 164 75

Following incubation of murine epidermis in medium containing either interleukin-2 or interleukin-6, there is significant upregulation in the density of Ia+ epidermal Langerhans cells (to 159% and 175% of control, respectively). This cytokine-induced upregulation is abrogated by either rabbit or human IgG due to triggering of Fc gamma receptors. In contrast, human IgA does not inhibit the effect of interleukin-2 or interleukin-6. Using different isotypes of murine IgG, we have demonstrated that all subclasses are capable of inhibiting the cytokine-induced enhancement of Ia antigen, although IgG1 and IgG2b must be heat aggregated to be effective. The IgG-mediated events are dependent on prostaglandin synthesis because they can be blocked by the cyclooxygenase inhibitor indomethacin, 10 micrograms/ml. The responsible PG appears to be PGD2; in contrast to its known inhibitory effect on macrophages, PGE2 does not inhibit the upregulation of Ia antigen on Langerhans cells. In addition, these IgG-mediated events are dependent upon the generation of cAMP because they can be blocked by the adenylate cyclase inhibitor 2',5'-dideoxyadenosine, 1 mM. Despite the apparently central role of PGD2 and cAMP in this process, triggering of the Fc gamma R by different isotypes of IgG blocks upregulation of Ia via at least two different pathways. The inhibition caused by aggregated IgG1 or IgG2b, which bind to Fc gamma RII on Langerhans cells, is abrogated by para-bromophenacylbromide, an inhibitor of phospholipase A2. In contrast, the inhibition caused by monomeric IgG2a, which binds to Fc gamma RI most likely on keratinocytes, or monomeric IgG3, which probably binds to this same Fc gamma RI, is abrogated by staurosporine, an inhibitor of protein kinase C, as well as by W7, a calmodulin antagonist. Finally, 1,2 dioctanoyl-rac-glycerol, an activator of protein kinase C, mimics the Ig-mediated events. Based on these findings, as well as studies using monoclonal antibodies to the murine Fc gamma receptors I and II, we conclude that, as is the case in murine macrophages, triggering of an epidermal Fc gamma RI, most likely on keratinocytes, results in the generation of cAMP via a Ca(++)-dependent protein kinase C pathway, whereas triggering of an epidermal Fc gamma RII, most likely on Langerhans cells, results in the elevation of cAMP via a phospholipase A2-mediated pathway. In contrast to the situation for macrophages, PGD2 is a vital intermediate in both pathways, perhaps because Langerhans cells have receptors for only this prostaglandin.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effect of triggering epidermal Fc gamma receptors on the interleukin-2- and interleukin-6-induced upregulation of Ia antigen expression by murine epidermal Langerhans cells: the role of prostaglandins and cAMP. 165 69


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