Pharmacodynamic effects of everolimus on anti-CD3 antibody-stimulated T-lymphocyte proliferation and interleukin-10 synthesis in stable kidney-transplant patients.
Author(s): Bohler T, Waiser J, Lichter S, Schumann B, Neumayer HH, Kamar N, Budde K
Affiliation(s): INSERM U858, I2MR, Eq. 10, Institut Louis Bugnard, Batiment L3, CHU Rangueil, 1 Avenue J Poulhes, 31403 Toulouse Cedex 4, France. firstname.lastname@example.org
Publication date & source: 2008-06, Cytokine., 42(3):306-11. Epub 2008 Apr 28.
Publication type: Clinical Trial, Phase I; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't
Everolimus (rapamycin derivative, RAD) is a new immunosuppressive drug that prevents allograft rejection. Herein, the pharmacodynamics of everolimus in human renal-allograft recipients is evaluated. Single doses of everolimus (0.75-10mg), combined with a maintenance immunosuppressive therapy based on CyA, decreased lymphocyte proliferation. In addition, the effect of multiple doses of everolimus (0.75-10mg) given daily for 21 days, to stable renal-allograft patients (n=11), was investigated. Everolimus treatment resulted in immediate inhibition (25-55%) of lymphocyte proliferation in renal-allograft recipients; values returning to baseline by 14 days after cessation of everolimus treatment. Placebo-treated patients showed no decrease in lymphocyte proliferation. Interestingly, everolimus reduced IL-10 synthesis by 20-60% in renal-allograft recipients. Phagocytosis rates were not changed by everolimus. In vitro, everolimus inhibited lymphocyte proliferation and IL-10 synthesis dose dependently in anti-CD3 mAb and LPS stimulated peripheral blood mononuclear cell cultures derived from human volunteers.