NEUTRALIZING IL-12 ACTIVITY AS A STRATEGY FOR PROLONGING ALLOGRAFT SURVIVAL AND PREVENTING GRAFT-VERSUS-HOST DISEASE

Interleukin-12 (IL-12) is a key immunoregulatory cytokine which promot es the development of Th1-dependent, cell-mediated immune responses. A cute allograft rejection after organ transplantation and acute graft-v ersus-host disease (GVHD) after bone-marrow transplantation are genera lly attributed to cell-mediated immune mechanisms and, therefore, pote ntially susceptible to immunological intervention at the level of IL-1 2. Recent data from murine models of transplantation have highlighted the potential of IL-12 as a selective target for immunotherapy. Neutra lising endogenous IL-12 for a brief period at the time of transplant p romotes long-term deviation from a Th1 to a polarised Th2 alloimmune r esponse. This confers lasting protection from GVHD but is less effecti ve at preventing acute rejection, possibly because Th2-dependent immun e responses are also capable of effecting graft rejection.