Blood lymphocytes of autoimmune disease patients receiving FK506 exhibit normal ex vivo cytokine gene expression and proliferative responses.
It is well recognized that FK506 (Tacrolimus) is a powerful inhibitor of CD4+ T-cell activation and proliferation in vitro. In this study, immunophenotypic and functional analyses were performed on peripheral blood mononuclear cells from a total of 30 patients with various autoimmune disorders before and whilst the patients were receiving systemic FK506 therapy. The expression of cell surface IL-2R alpha and -beta on CD4+ and CD8+ cells, cytokine message (IL-2, IFN-gamma, IL-4, IL-10) and the proliferative activity of lymphocytes in response to rIL-2 were examined. Despite plasma levels of FK506 compatible with the blockade of IL-2 production by stimulated T cells in vitro, cells from patients on FK506 treatment cultured ex vivo with either ConA or IL-2 did not differ from normal cells in their expression of cytokine mRNA or their proliferative responses. These data indicate that the presumed in vivo suppression of T-cell function by FK506 is rapidly reversible ex vivo. Alternatively/additionally, they suggest that FK506 may mediate its in vivo action primarily by mechanisms other than blockade of T-cell function.
Lemster
B
B
Department of Surgery, University of Pittsburgh Medical Center, PA 15213.
Woo
J
J
Thomson
A W
AW
D000293:Adolescent; D000328:Adult; D000368:Aged; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000276:immunology*; D016516:CD4-CD8 Ratio / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D016827:CD8 Antigens / Q000097:blood; D016207:Cytokines / Q000187:drug effects*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007376:Interleukin-2; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000187:drug effects*; D016559:Tacrolimus / Q000494:pharmacology*
D016827:CD8 Antigens; D016207:Cytokines; D007376:Interleukin-2; D016559:Tacrolimus