Orale Glukokortikoide

Reducing the Toxicity of Long-Term Glucocorticoid Treatment in Large Vessel Vasculitis

“…They form a complex with the cytosolic GC-receptor, and the hormone-receptor complex binds to specific DNA sites causing “transactivation”. This results in an increased synthesis of anti-inflammatory proteins such as IL-10, annexin-1, or inhibitors of nuclear factor Kappa B (NFκB) [ 15 , 19 ]. Of note, transactivation is (possibly oversimplistically) responsible for most GC-associated AEs [ 17 , 19 , 20 ].…”

“…This results in an increased synthesis of anti-inflammatory proteins such as IL-10, annexin-1, or inhibitors of nuclear factor Kappa B (NFκB) [ 15 , 19 ]. Of note, transactivation is (possibly oversimplistically) responsible for most GC-associated AEs [ 17 , 19 , 20 ]. At the same time, the hormone-receptor complex inhibits pro-inflammatory transcription factors causing “transrepression”, e.g., inactivation of NFκB [ 17 ].…”

“…Non-genomic effects are mainly mediated by non-specific interactions with cellular membranes, specific interactions with membrane-bound GC-receptors, and further effects mediated by the cytosolic GC-receptor [ 16 – 18 ]. Compared with the genomic effects outlined above, non-genomic effects (a) appear more quickly (seconds-minutes) [ 15 , 19 ], (b) come into play only at high dosages (beginning at approximately ≥ 30–100 mg/day prednisone equivalent) [ 17 , 20 ], and (c) do not have such strong “ceiling effects” [ 18 , 20 ]. Non-genomic effects are especially desired in acute situations, e.g., in anaphylaxis or complicated GCA [ 19 ].…”