FK-506 AND CYCLOSPORINE-A (CSA) IMMUNOMODULATION OF THE HUMAN GUT MUCOSAL IMMUNE-SYSTEM

FK-506 and cyclosporine A (CsA) are two immunosuppressive drugs used i n the treatment of patients after liver and small intestine transplant ation. A clinical advantage of FK-506 over CsA has been observed in th ese patients. Although the immunomodulation of bath drugs has been wel l documented in the circulatory immune system, their effect on the muc osal immune system is not well established. In this study, the effect of FK-506 on the human gut mucosal immune system was compared to CsA. Proliferation of human colonic lamina propria lymphocytes (LPL) was me asured by DNA synthesis and ornithine decarboxylase (ODC) activity. Re sults show that FK-506 and CsA suppress LPL DNA proliferation in a dos e-dependent manner. FK-506 had a stronger antiproliferative effect com pared to CsA. Moreover, the antiproliferative effect of both drugs was not dependent on monocytes or monocyte-associated factors (IL-1 beta, IL-6). In addition, exogenous addition of IL-2 did not restore the su ppressive effect of either drug on LPL DNA synthesis. We conclude that : (1) both drugs have an antiproliferative effect on the human mucosal immune system; and (2) the stronger effect of FK-506 on human LPL com pared to CsA may explain its superior clinical response observed in pa tients after liver/small intestine transplantation.