Tacrolimus and sirolimus

What are tacrolimus and sirolimus?

Tacrolimus is a macrolide produced by a fungus (actinomycete). It has immunosuppressive effects similar to cyclosporine but at a dose 10 to 100 times lower (0.1–0.25 mg/kg per day; usual dose 2–5 mg BID). Tacrolimus, like cyclosporine, is a potent inhibitor of T-cell activation and inhibits transcription of early T-cell activation genes, such as IL-2, by interfering with the binding of nuclear regulatory factor, NF-AT, to its target region in the enhancer region of these inducible genes (see Question 13). Notably, tacrolimus causes less increase in uric acid than cyclosporine and it may be useful to switch from cyclosporine to tacrolimus in transplant patients with tophaceous gout. Tacrolimus has shown efficacy particularly in treatment-refractory myositis with or without lung involvement.

Sirolimus (rapamycin) and its derivative, everolimus (Afinitor), inhibit T-cell proliferation by binding to its cytoplasmic immunophilin (FK-binding protein, TOR, or FRAP), which inhibits IL-2 receptor transduction events after the receptor has bound IL-2. This blocks progression of the T-cell cycle from G1 to S phase. Sirolimus has not been used much in the treatment of rheumatic diseases.


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