Yin and yang of cytokine regulation in solid organ graft rejection and tolerance

Solid organ transplantation is the therapy of choice for end stage diseases. The alloimmune response generated after transplantation induces the production of a "cytokine storm" that can lead to either the rejection of the organ or graft acceptance. These key decisions, which determine the transplant fate, depend on the type of cytokine response (Th1/Th2). An inflammatory response will lead to graft loss; a tolerogenic response assists in graft acceptance. A balance between different factors often determines outcome. The same cytokine may assist in either allograft rejection or graft survival depending on: (1) the cell types in the vicinity, (2) the amount of each cytokine produced, (3) different sites, and (4) if it acts in a synergistic or antagonistic manner with other cytokines. This review focuses on cytokines that manipulate the alloimmune response after organ transplantation and that play a role either in graft rejection (yin) or tolerance (yang).