Neutralising 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 promotes the development of Thl-dependent, cell-mediated immune responses. Acute allograft rejection after organ transplantation and acute graft-versus-host disease (GVHD) after bone-marrow transplantation are generally attributed to cell-mediated immune mechanisms and, therefore, potentially susceptible to immunological intervention at the level of IL-12. Recent data from murine models of transplantation have highlighted the potential of IL-12 as a selective target for immunotherapy. Neutralising endogenous IL-12 for a brief period at the time of transplant promotes long-term deviation from a Th1 to a polarised Th2 alloimmune response. This confers lasting protection from GVHD but is less effective at preventing acute rejection, possibly because Th2-dependent immune responses are also capable of effecting graft rejection.
Orr
D J
DJ
Department of Surgery, Western Infirmary, Glasgow.
Bolton
E M
EM
Bradley
J A
JA
D016026:Bone Marrow Transplantation / Q000276:immunology; D006084:Graft Rejection / Q000503:physiopathology; D006085:Graft Survival / Q000502:physiology; D006086:Graft vs Host Disease / Q000517:prevention & control*; D006801:Humans; D018664:Interleukin-12 / Q000627:therapeutic use*; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology
D018664:Interleukin-12