Interleukin-10 modulation of alloreactivity and graft-versus-host reactions.

Abstract

BACKGROUND The biological properties of interleukin (IL)-10 in tolerance induction and inhibition of alloreactivity have suggested a therapeutic use of this cytokine as an additional or alternative prophylaxis for graft-versus-host disease (GvHD). However, the effects of exogenous IL-10 on GvHD are mainly studied in animal models, and the results remain conflicting. This study aims to demonstrate, for the first time, whether the addition of exogenous IL-10 can reduce the severity of graft-versus-host reactions (GvHR) in humans. METHODS The regulatory role of exogenous IL-10 in GvHR was investigated using an in vitro human skin explant model. The effects of IL-10 on skin GvHR were tested in parallel with allo-antigen induced T-cell proliferation, cytolytic reactivity, and cytokine production. RESULTS In the presence of IL-10, the mixed lymphocyte reaction (MLR) primed responder cells showed significantly lower proliferative and cytolytic responses compared with the responder cells from the control MLR carried out in the absence of IL-10. The responder cells from IL-10 containing MLR induced significantly less severe skin GvHR and displayed a significantly reduced T-cell activation and cytokine production. A significant correlation was observed between the levels of TNF-alpha production and the sensitivity to IL-10 modulation of GvHR. CONCLUSIONS The addition of exogenous IL-10 strongly inhibited the broad alloreactivity initiated by primary MLR and significantly reduced the overall severity of skin GvHR induced by MLR primed responder cells. Responder cells producing high TNF-alpha following allogeneic stimulation appeared to be less sensitive to IL-10 modulation of GvHR.