Immunologic glucocorticoids

Immunologic Glucocorticoids can cause hypersensitivity reactions. An anaphylactic reaction to intravenous methylprednisolone during anesthesia has been reported, with positive skin tests and a positive basophil activation test [18 ]. 

Glucocorticoids have become important agents for use in the treatment of many inflammatory, immunologic, hematologic, and other disorders. This has stimulated the development of many synthetic steroids with anti-inflammatory and immunosuppressive activity. 

Garvy, B A, Telford, W. G., King, L E., and Fraker, P J (1993) Glucocorticoids and irradiation-induced apoptosis in normal munne bone marrow B-hneage lymphocytes as determined by flow cytometry. Immunology 76, 270-277... 

Since the glucocorticoids have immunosuppressive and anti-inflammatory properties, one would not expect allergic reactions to be a problem, except when excipients act as allergens. Nevertheless, allergic reactions to glucocorticoids themselves have been reported (SEDA-21, 419 291). Immunological reactions to glucocorticoids have... 

The authors of the last report commented that generalized delayed type hypersensitivity to systemic administration of a glucocorticoid is rare. Despite the potent immunosuppressive effect of glucocorticoids on immunocompetent cells, the clinical features, the skin biopsy specimen, and the positive delayed skin test reactions strongly suggested an immunological mechanism T cells were clearly involved and the high concentrations of interleukins 5, 6, and 10 were consistent with a T helper type 2 reaction. The raised concentrations of interleukin-5 were probably responsible for the blood and tissue eosinophilia. 

Since glucocorticoids reduce the immunological defences of the body to most types of infection, their use in the eyes should be monitored carefully. When longterm use is necessary, even with oral or inhalation therapy, eye examination should be performed every 6 months. The ophthalmological follow-up of patients using topical glucocorticoids should include tonometry at least twice a year, careful slit-lamp examination for... 

Immunological Mediators Whose Production or Actions Can Be Blocked by Glucocorticoids... 

Nieto MA Lopez-Rivas A (1989) IL-2 protects T lymphocytes from glucocorticoid-induced DNA fragmentation and cell death. Journal of Immunology 143 4166-4170. 

Laue, L., Lotze, M.T., Chrousos, G.P., Barnes, K., Loriaux, D.L. and Fleisher, T.A. (1990) Effect of chronic treatment with the glucocorticoid antagonist RU 486 in man toxicity, immunological, and hormonal aspects. Journal of Clinical Endocrinology and Metabolism, 71, 1474-1480. 

Lee SW, Tsou AP, Chan H, et al. Glucocorticoids selectively inhibit the transcription of the interleukin ip gene and decrease the stability of interleukin ip mRNA. Immunology 1988 85 1204-1208. 

A variety of debilitating diseases, such as rheumatoid arthritis, inflammatory myopathies, cancers, and a variety of immunological diseases are treated with the classic synthetic glucocorticoids, dexamethasone, and prednisone. However, long-term treatment with these drugs often leads to serious side effects such as fat redistribution, diabetes, vascular necrosis, and osteoporosis. There is currently an intense effort to identify new small molecules that are able to differentially modulate GR to retain the beneficial effects of glucocorticoids and reduce the incidence of unwanted side effects [10]. 

Systemic exposure to denileukin diftitox is variable but proportional to dose. It has a distribution t 2 of 2-5 minutes with a terminal t of 70 minutes. Immunologic reactivity to denileukin diftitox can be detected in virtually all patients after treatment but does not preclude clinical benefit with continued treatment. Denileukin diftitox clearance in later cycles of treatment is accelerated by two- to threefold as a result of development of antibodies, but serum levels are greater than required to produce cell death in IL-2R-expressing cell lines (1-10 ng/mLfor more than 90 minutes). Patients with a history of hypersensitivity reactions to diphtheria toxin or IL-2 should not be treated. Significant toxicities associated with denileukin diftitox are acute hypersensitivity reactions, a vascular leak syndrome, and constitutional toxicities glucocorticoid premedication significantly decreases toxicity. 

Immunosuppressive effects Glucocorticoids inhibit some of the mechanisms involved in cell-mediated immunologic functions, especially those dependent on lymphocytes. These agents are actively lymphotoxic and are important in the treatment of hematologic cancers. The drugs do not interfere with the development of normal acquired immunity but delay rejection reactions in patients with organ transplants. 

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