The effects of FK506 on refractory inflammatory myopathies.

We performed an observational clinical study, the effects of tacrolimus (FK506) on the thymic output in patients with refractory inflammatory myopathies. Sixteen patients with polymyositis (PM) and 15 with dermatomyositis (DM) were treated orally with tacrolimus. Serum CK levels significantly decreased 2 to 4 months after tacrolimus therapy (p < 0.01), and MRC (Medical Research Council) scores were significantly improved 2 months after tacrolimus therapy (p < 0.01). T-cell receptor excision circle (TREC) content, a proxy for thymic export was not significantly different from that in age-matched controls, except for an increase in the TREC content within CD8+ single positive cells in patients with DM. TREC contents within double-positive cells and CD4+ single-positive cells were significantly decreased 4 M after tacrolimus therapy (p < 0.05) in PM/DM patients. Tacrolimus treatment significantly attenuated TREC content within cultured CD4+CD8- cells from PM/DMpatients (p < 0.05), but total cell counts were not significantly changed. These results indicate that tacrolimus therapy suppresses not only activated T-lymphocytes, but also some naïve T-cell subsets in both PM and DM.