Effects of an immunosuppressant, FK506, on interleukin 1 alpha production by human macrophages and a macrophage-like cell line, U937.
A recently discovered immunosuppressive agent, FK506, has been shown to be effective primarily as an inhibitor of T cell responses in vitro, but little is known about its effects on accessory cell function. This study was undertaken to determine the effect of FK506 on interleukin 1 (IL-1) production by macrophages, by using a sensitive and specific enzyme-linked immunosorbent assay. FK506 partially suppressed IL-1 alpha release, from macrophage-like U937 cells stimulated with phorbol myristate acetate and from human monocytes and alveolar macrophages activated with lipopolysaccharide, in a dose-dependent manner. Moreover, it was indicated that FK506 suppressed not only IL-1 release but also IL-1 synthesis itself, by measurement of cell-associated IL-1 alpha of U937 cells. The optimal concentrations of FK506 for suppressing IL-1 alpha did not affect cell viability or proliferation, and were 10- to 100-fold lower than those of cyclosporin A. It is concluded that FK506 affects macrophage physiology, suppressing IL-1 alpha production significantly. Thus, FK506 has the potency to act on non-T cells and the effect on macrophages may play an additional role in preventing graft rejection.
Keicho
N
N
Third Department of Internal Medicine, University of Tokyo, Japan.
Sawada
S
S
Kitamura
K
K
Yotsumoto
H
H
Takaku
F
F
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003524:Cyclosporins / Q000494:pharmacology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007375:Interleukin-1 / Q000096:biosynthesis*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism; D016559:Tacrolimus
D000900:Anti-Bacterial Agents; D003524:Cyclosporins; D007166:Immunosuppressive Agents; D007375:Interleukin-1; D016559:Tacrolimus