TGF-β in renal allograft rejection

The role of TGF-beta 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-beta, receptor, and message have all been documented to be elevated in the tubulointerstitium, likely a reflection of TGF-beta's role in recruiting leukocytes to areas of injury and downregulation of the inflammatory response. In chronic rejection, expression of TGF beta, message, and induced proteins is elevated, especially in cortex. TGF-beta 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-beta 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.