PPARα Ligand WY14643 Reduced Acute Rejection After Rat Lung Transplantation With The Upregulation of IL-4, IL-10 and TGFβ mRNA Expression

Background: The peroxisome proliferators-activated receptor-alpha (PPAR alpha) is important in lipid metabolism and regulation of inflammation. Recent studies have demonstrated the immunoregulatory effects of PPAR alpha. This investigated the immunosuppressive effects of PPAR alpha using its ligand, WY14643, on acute lung allograft rejection in a rat model and its mechanism of action. Method: The left lungs were transplanted orthotopically from Brown-Norway donors to F344 recipients. The recipients were then divided into control and WY14643 treatment groups. The allograft rejection was evaluated by daily chest Xray imaging and was evaluated histologically on Day 7 after transplantation. The cytokine messenger RNA (mRNA) expression at Days 3 and 5 were also evaluated in allografts and recipient spleens. Results: The radiologic and histologic findings indicated that treatment with the WY14643 reduced acute allograft rejection. WY14643 also significantly extended the allograft survival time. This amelioration of acute rejection by WY14643 was also associated with up-regulated interleukin (IL)-4, IL-10, and transforming growth factor-beta (TGF beta) mRNA expression in the lung allografts and spleens. Conclusion: This study demonstrated that the administration of the PPARa ligand, WY14643, ameliorates acute lung allograft rejection in rats. Treatment with WY14643 reduced histopathologic scores, prolonged graft survival, and up-regulated the expression of anti-inflammatory cytokine IL-4, IL-10, and TGF beta mRNA compared with the control. J Heart Lung Transplant 2009;28:1172-9. Copyright (C) 2000 by the International Society for Heart and Lung Transplantation.