Role of cytokines in allograft rejection

This review examines the evidence, both from experimental models and numerous clinical settings, that has suggested that suppression of acute allograft rejection correlates with a relative decrease in type-1 cytokine production and an increase in type-2 cytokine production. This correlation has spurred studies on cytokine gene polymorphisms, to assess evidence that certain cytokine-producing genotypes are associated with increased incidence of transplant rejection, and also an interest in the value of monitoring cytokine profiles post-transplantation in long-term follow-up of transplant patients. An appraisal is given of the potential for cytokine gene therapy in transplantation, using both dendritic cells (DC) and graft tissue itself as target cells. Along the same lines, gene-targeting of DCs to increase or decrease expression of molecules (CD40/CD80/CD86/CD200) believed to control the polarization of T cell development (and cytokine production) is discussed. The review concludes with consideration of the possibility that one future goal of the pharmaceutical industry will be to develop novel immunosuppressants with selective inhibitory action on the production of distinct cytokines.