Effect of a new immunosuppressive agent, FK506, on human lymphocyte responses in vitro. II. Inhibition of the production of IL-2 and gamma-IFN, but not B cell-stimulating factor 2.

The mechanism whereby FK506 inhibits immune responses was assessed in in vitro human studies. FK506 inhibited in a dose-dependent manner both interleukin 2 and gamma-interferon secretion of PBMC stimulated with PHA. Complete inhibition was obtained at the concentration of 0.25 nM of FK506 for IL-2 and 1 nM of FK506 for gamma-IFN production. Inhibition of 50% (IC50) was detected with 0.06 nM for IL-2 and 0.25 nM for gamma-IFN production. On the other hand, FK506 could not inhibit the B cell-stimulating factor 2 (BSF-2) production of PBMC, indicating the possibility that FK506 might spare the B cell function. Cloned T cells and cloned B cells, once activated, were scarcely affected by the agent; neither IL-2-driven proliferation of cloned T cells nor BSF-2-driven proliferation of cloned B cells was inhibited by FK506 at any concentration.