Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0338671 (Steroids)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this review emphasis is put on the mechanisms for the antiinflammatory and immunoregulatory role of glucocorticoids in man. Glucocorticoids have numerous effects some of which are permissive; steroids are thus important not only for what they do, but also for what they permit or enable other hormones and signal molecules to do. Some important effects are the result of altered protein synthesis due to steroidreceptor complex formation. One such protein is macrocortin which is induced by glucocorticoids. Macrocortin inhibits the enzyme phospholipase A2, thereby reducing the formation of prostaglandins and leukotriens. Steroids also reduce the release or synthesis of plasminogen activator and certain cytokines such as interleukin 1 and macrophage migration inhibitory factor. Glucocorticoids inhibit the release of histamin and lysosomal constituents of possible importance for the inflammatory response. In addition, steroids have profound effects on the circulation and distribution of white blood cells.
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PMID:Antiinflammatory and immunoregulatory effects of glucocorticoids: mode of action. 307 81

The body's response to infection/inflammation is initiated by the elaboration of cytokines, such as tumor necrosis factor, interleukin 1-beta (IL-1-beta), IL-6, and IL-8. Cytokines, in turn, stimulate the pituitary-adrenal axis, and it has been suggested that the corticosteroids elaborated serve as negative feedback signals to diminish inflammatory events. To test this hypothesis, we administered hydrocortisone shortly before endotoxin administration to normal volunteers. Steroids greatly reduced the clinical response to endotoxin and attenuated the appearance of tumor necrosis factor, IL-6, and IL-8 in the circulation. In contrast, IL-1-receptor antagonist, a competitive antagonist of the IL-1 receptor, was unaffected by steroid administration. These data suggest that IL-1-receptor antagonist may act in synergism with corticosteroids to reduce inflammation. Elevation of concentrations of these two factors, corticosteroids and IL-1-receptor antagonist, in plasma appears to be the mechanism used by the body to overcome the effects of inflammatory cytokines.
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PMID:Elaboration of interleukin 1-receptor antagonist is not attenuated by glucocorticoids after endotoxemia. 843 Nov 15

Graves' ophthalmopathy is an autoimmune disease manifested as exophthalmus, lid lag and diplopia. As in the accompanying autoimmune thyroid disease, there is an autoimmune homonal and cellular attack on the orbita, mainly the retro-orbital tissues. Steroids are the cornerstone of therapy. We reviewed the evidence for a similar therapeutic effect of i.v., immunoglobulins (IVIGs) and their better side affect profile as compared to steroids. We also described an impressive therapeutic success with IVIG given to a patient with resistant ophthalmopathy. The clinical picture of Graves' ophthalmopathy is attributed to a pathologic hyper--activation of orbital fibroblasts, deposition of collagen and glycosaminoglycans in the extra-cellular matrix and eventually fibrosis. These are mediated by leucoregulin, IL-1, IFN-gamma, and TGF-beta--all secreted by lymphocytes and mast cells in the retorbital space. Another mode of cell activation is by binding of autoantibodies (presumably thyroid stimulating Ab's) to an antigenic determinant on the surface of fibroblasts. I.v. immunoglobulins, known today to be active in a variety of autoimmune processes, exert their effect on autoantibodies, complement, phagocytic cells etc. IVIGs also inhibit orbital lymphocytes and fibroblasts through inhibition of IL-1 or/and TGF-beta.
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PMID:[Intravenous immunoglobulins treatment of patients with Graves' ophthalmopathy]. 1141 58

We investigated the effect of interleukin 1beta (IL-1beta) on steroid sulfatase (STS) activity and the expression of STS mRNA in human endometrial stromal cells. Endometrial tissue samples were obtained from patients undergoing hysterectomy to remove uterine fibroids. Stromal cells were isolated from the tissue preparation and cultured. IL-lbeta (1 approximately 100 ng/ml) was added into the culture medium and incubated for 24 h. The expression of STS mRNA was measured by competitive RT-PCR. The addition of IL-lbeta at 10 and 100 ng/ml suppressed STS mRNA expression to 55.2 +/- 12.8% and 25.1 +/- 10.9%, respectively, of the control sample to which no IL-lbeta had been added. STS activity was measured by radiolabelled steroid metabolite using thin layer chromatography, and this activity was also significantly suppressed in response to the administration of IL-lbeta in a dose-dependent manner. When IL-1 receptor antagonist (IL-1ra) was added together with IL-1beta to the culture medium, mRNA expression and STS activity were recovered. The present study is the first to demonstrate IL-1beta regulation of STS activity locally in human endometrium. IL-1beta suppressed mRNA and activity of STS in stromal cell culture. This initial demonstration of IL-1beta regulation of STS implies that IL-1beta may control the steroid microenvironment in human uterine endometrium by reducing biologic action of estrogen.
Steroids 2002 Jun
PMID:Regulation of estrogen activity in human endometrium: effect of IL-1beta on steroid sulfatase activity in human endometrial stromal cells. 1199 39

Alcoholic hepatitis (AH) is a severe form of alcoholic liver disease with high mortality. The pathogenesis of AH is not fully understood, but it is generally believed that inflammation is a key factor leading to liver failure in AH. Steroids, which have broad immunosuppressive effects, have been used for the treatment of AH over the last forty years. Steroids elicit modest improvement in short-term survival rate in patients with severe AH, but also cause severe side effects. Several specific inflammatory targets (e.g., IL-1, LPS, and gut microbiota) are currently under investigation for the treatment of AH with the goal to obviate or reduce steroid administration. In addition to inflammation, impaired liver regeneration is another major cause of liver failure in AH, which deteriorates further after steroid treatment because inflammation plays a key role in promoting liver repair. Interleukin-22 (IL-22) is a promising drug for the treatment of AH because of its hepatoprotective and anti-fibrotic functions and relatively few known side effects. In addition, IL-22 treatment also ameliorates bacterial infection and kidney injury, two major complications associated with severe AH. IL-22 is currently under investigation in preclinical and clinical studies and may hold great promise for AH by providing more beneficial effects and fewer side effects than current therapies.
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PMID:Combination therapy: New hope for alcoholic hepatitis? 2619 67