A review of the action of tacrolimus (FK506) on experimental models of rheumatoid arthritis.
Tacrolimus (FK506) is an immunosuppressive drug, widely used for organ transplantation and atopic dermatitis. Tacrolimus exerts its immunosuppressive effects primarily by interfering with the activation of T cells, via inhibition of calcineurin. Recent clinical studies have also demonstrated the efficacy of tacrolimus in the treatment of rheumatoid arthritis (RA), an autoimmune disease in which T cells play a pivotal role in pathogenesis. Inflammatory cytokines such as TNF-alpha, IL-1 beta, and IL-6 are involved in development of the disease. Recently, modes of action of tacrolimus on RA have been intensively studied in in vitro and animal arthritis models, demonstrating that tacrolimus exerts various novel actions as an anti-rheumatic drug. The pharmacological action of tacrolimus suggests that it has potential to specifically suppress the production of pathogenic inflammatory cytokines with a low frequency of infection, improve joint inflammation and bone/cartilage destruction, fully recover loss of functional status, exert rapid relief in arthritic pain, and promote osteogenic and chondrogenic differentiation. Here we review the action of tacrolimus on experimental models of RA, with a focus on our recent studies, and provide further insight into experimental models used for identifying efficacious anti-rheumatic drugs.
Miyata
S
S
Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., 2-1-6, Kashima, Yodogawa-ku, Osaka, 532-8514, Japan. susumu_miyata@po.fujisawa.co.jp
Ohkubo
Y
Y
Mutoh
S
S
D000700:Analgesics / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002356:Cartilage / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D016559:Tacrolimus / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*
D000700:Analgesics; D016207:Cytokines; D016559:Tacrolimus