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.
Yoshimura
N
N
Second Department of Surgery, Kyoto Prefectural University of Medicine, Japan.
Matsui
S
S
Hamashima
T
T
Oka
T
T
D000328:Adult; D002460:Cell Line; D002999:Clone Cells / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007371:Interferon-gamma / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000494:pharmacology; D015850:Interleukin-6; D007378:Interleukins / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology; D011725:Pyridines / Q000494:pharmacology*; D016559:Tacrolimus
D007166:Immunosuppressive Agents; D007376:Interleukin-2; D015850:Interleukin-6; D007378:Interleukins; D011725:Pyridines; D007371:Interferon-gamma; D016559:Tacrolimus