The anti-inflammatory and immunosuppressive effects of corticosteroids

The anti-inflammatory and immunosuppressive effects of corticosteroids are dose-dependent and occur at high doses. These effects are mediated by genomic mechanisms and non-genomic mechanisms. Genomic mechanisms are where there will be alterations in gene transcription of substances that mediate the inflammatory response. There is suppression of the transcription pro-inflammatory factors such as nuclear factor-κB [NF-κB], activator protein-1, and interferon regulatory factor-3 and activation of transcription of factors promoting production of anti-inflammatory cytokines such as IL-10, NF-κB inhibitor, and lipocortin-1. These occur over a period of time. Non-genomic mechanisms are seen at high doses of glucocorticoids. At high doses, glucocorticoids bind the membrane-associated glucocorticoid receptors on target cells such as T-lymphocytes, resulting in impairment of receptor signaling and immune response of the T lymphocytes. High-dose glucocorticoids also interact with the cycling of calcium and sodium across the cell membrane causing a quick decrease in inflammation.
2) Glucocorticoids bind to mineralocorticoid receptors (MRs) and produce their mineralocorticoid effect (i.e., increasing sodium and decreasing potassium), but only when used at the high dose and for an extended period. Thus, there will be water retention, not water excretion.
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