MURINE IL-10 FAILS TO REDUCE GVHD DESPITE INHIBITION OF ALLOREACTIVITY IN-VITRO

Graft-versus-host disease (GVHD) is a serious complication following a llogeneic bone marrow transplantation (BMT), Initial immunologic event s that are thought to lead to clinical GVHD include allogeneic antigen presentation, CD4(+) T cell proliferation and eventually generation o f specific cytotoxic lymphocytes. Interleukin-10 (IL-10) has been show n to inhibit the function of antigen presenting cells (APC) and to red uce lymphocyte proliferation. In this study we investigated the possib le role of recombinant murine IL-10 (rmIL-10) as prophylactic treatmen t of GVHD in a murine BMT model involving B10.BR donor mice (H-2(k)) a nd AKR recipients (H-2(k)), In particular, we wished to determine whet her early post-BMT administration of IL-10 would suppress GVHD by inte rfering with macrophage function and inflammatory cytokine production during the proposed 'afferent' phase of GVHD, In MLR assays, rmIL-10 s ignificantly inhibited the proliferation of donor spleen cells when st imulated by irradiated recipient spleen cells in a dose-dependent mann er, In murine BMT, rmIL-10 was administered exogenously by intraperito neal injection of 100 U daily in two different dosage schedules, on da ys -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 alp ha levels on day 3 (12 pg/ml vs 64 pg/ml in controls, P < 0.05), sugge sting that both macrophage function and inflammatory cytokine producti on were inhibited, In contrast to the MLR data, no significant improve ment in morbidity and mortality from GVHD was observed, Therefore, IL- 10 does not appear to be useful in GVHD prophylaxis.