Murine IL-10 fails to reduce GVHD despite inhibition of alloreactivity in vitro.

Graft-versus-host disease (GVHD) is a serious complication following allogeneic bone marrow transplantation (BMT). Initial immunologic events that are thought to lead to clinical GVHD include allogeneic antigen presentation, CD4+ T cell proliferation and eventually generation of specific cytotoxic lymphocytes. Interleukin-10 (IL-10) has been shown to inhibit the function of antigen presenting cells (APC) and to reduce lymphocyte proliferation. In this study we investigated the possible role of recombinant murine IL-10 (rmIL-10) as prophylactic treatment of GVHD in a murine BMT model involving B10.BR donor mice (H-2k) and AKR recipients (H-2k). In particular, we wished to determine whether early post-BMT administration of IL-10 would suppress GVHD by interfering with macrophage function and inflammatory cytokine production during the proposed "afferent' phase of GVHD. In MLR assays, rmIL-10 significantly inhibited the proliferation of donor spleen cells when stimulated by irradiated recipient spleen cells in a dose-dependent manner. In murine BMT, rmIL-10 was administered exogenously by intraperitoneal injection of 100 U daily in two different dosage schedules, on days-1, 0, 1, 2, 3, 6 to target the early post-BMT phase, and days-1, 0, 3, 5, 7, 10 after BMT, to administer the same total dose throughout the engraftment period. IL-10 injected mice had lower plasma IL-1 alpha levels on day 3 (12 pg/ml vs 64 pg/ml in controls, P < 0.05), suggesting that both macrophage function and inflammatory cytokine production were inhibited. In contrast to the MLR data, no significant improvement in morbidity and mortality from GVHD was observed. Therefore, IL-10 does not appear to be useful in GVHD prophylaxis.