Immunosuppression steroid-induced

In addition to the suppression of the hypophysial-pituitary axis and adrenal atrophy, these drugs can cause a variety of adverse effects, including osteoporosis, pancreatitis, steroid-induced diabetes mellitus, cataracts, glaucoma, psychosis, oral candidiasis and other opportunistic infections, immunosuppression, infertility, weight gain, and skin atrophy. Severe edema may also be produced, particularly in the face, depending on the degree of mineralocorticoid activity. 

Three endogenous opioids have been identified enkephalins, dynorphins and beta-endorphins. These opioid peptides selectively bind to the seven transmembrane GPCRs delta (8), kappa (k), and mu (p). Although dynorphin binds predominately to the k receptor, P-endorphines and enkephalins bind to p and 8 opioid receptors. It is important to note that the analgesia induced by opioids is mediated predominately throngh the p opioid receptor. In vitro studies have shown a decrease in the immnne function and proliferation following p-endorphin administration in rodents (Ray and Cohn 1999) and that the immunosuppressive effects by P-endorphins are steroid-independent (Berkenbosch et al. 1984 Nelson et al. 2000). 

An indirect proof of the role exerted by gut bacteria in the pathogenesis of NSAID enteropathy is represented by the similarities between indomethacin-induced intestinal damage and Crohn s disease [234, 246], Not only are these lesions anatomically (both macro- and microscopically) similar [246], but also sensitive to the same drugs, e.g. sulfasalazine [234,247], steroids [234,247], immunosuppressive compounds [248], and antibiotics [234-237],... 

Clinical use To induce remission of moderate to severe IBD. Once clinical remission is induced, steroids must be tapered. Other uses acute asthma exacerbations, arthritis, collagen diseases, immunosuppression for organ transplantation. 

MHC class Il-positive PMN were only found in the patients with active disease, but not in patients under immunosuppressive therapy or patients with inactive disease [37, 38] (fig. 2a). In fact, when patients with active disease were receiving immunosuppressive drugs, the MHC class II expression declined within a day or two (data summarized in fig. 2b). These data are consistent with the fact that PMN of patients receiving low-dose corticoids cannot be induced to upregulate MHC class II in vitro in response to IFN-y or GM-CSF [38] and that steroids prevent the upregulation of MHC class II antigens on PMN of healthy donors (fig. 2c). 

Both lymphotactin and fractalkine are expressed in an activation-dependent manner. The expression of lymphotactin is upregulated by phorbol ester and concanavalin 1 in T-cells isolated from peripheral blood (Middel et al., 2001). It can be inhibited by anti-inflammatory steroid dexamethasone or immunosuppressive drugs such as cyclosporine A and FK506 (Middel et al., 2001). These agents also regulate the expression of lymphotactin receptor XCRl on T-cells in a manner similar to the regulation of lymphotactin expression. The nuclear factor of activated T-cells (NF-AT) family s transcription factors are likely to be involved in the activation-induced expression and cyclosporine A-dependent inhibition of lymphotactin (Yoshida et al., 1999). 

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