TGF-β in Renal Allograft Rejection

The role of TGF-β in pathological processes in the transplanted kidney is beginning to be investigated both in animal models and in humans. In both settings in acute cell-mediated rejection, TGF-β, receptor, and message have all been documented to be elevated in the tubulointerstitium, likely a reflection of TGF-β’s role in recruiting leukocytes to areas of injury and downregulation of the inflammatory response. In chronic rejection, expression of TGF-β, message, and induced proteins is elevated, especially in cortex. TGF-β mRNA, unlike other inflammatory cytokine mRNAs, correlated very well with interstitial fibrosis, a hallmark of chronic rejection. Thus, a relationship between renal scarring and TGF-β has been documented by most studies of transplant kidneys. Additionally, this growth factor also appears to have a role in the renal fibrosis associated with cyclosporine administration and perhaps in augmenting this drug’s immunosuppressive effects.