Tacrolimus (FK 506)

Objective: The focus of this review is to summarize the mechanism of action, animal and clinical studies, and adverse effects of tacrolimus (FK 506) in treatment after solid organ transplantation and in treatment of autoimmune diseases. Data sources: A detailed search of the literature was done. Both human and animal studies considered relevant and important were used. Study selection: Material was taken only from peer reviewed journals. Results: FK 506 is a macrolide lactone antibiotic with potent immunosuppressive activity. It acts primarily on CD4+ T helper lymphocytes by inhibiting the production of lymphokines, which are required for cell growth and differentiation, principally interleukin-2, at the transcriptional level. It was first clinically used in patients after liver transplantation. Tacrolimus-based immunosuppression has been proven to be beneficial in prolonging the survival of liver, kidney, heart, lung, pancreas, pancreatic islet, and intestinal allografts. Autoimmune diseases in which the immunosuppressive efficacy of tacrolimus has been tested experimentally include arthritis, systemic lupus erythematosus, uveitis, type-1 diabetes, thyroiditis, autoimmune renal disorders, experimental autoimmune encephalomyelitis, myocarditis, myasthenia gravis, colitis, and alopecia areata. Tacrolimus has been used for treatment of selected human diseases, such as psoriasis, uveitis, corticosteroid-resistant nephrotic syndrome, recalcitrant pyoderma gangrenosum, new onset type 1 diabetes, autoimmune chronic active hepatitis, pediatric autoimmune enteropathy, Crohn's disease and atopic dermatitis. Conclusion: Tacrolimus is a potent immunosuppressive drug in treatment of patients after solid organ transplantation and in selected autoimmune diseases. Further studies are necessary to better understand intracellular mechanism of action and specify therapeutic indications.