European Journal of Cardio-thoracic Surgery 13 (1998) 424–430 Transforming growth factor-b1 and lung allograft fibrosis1

Objectives: Transforming growth factor b1 (TGF-b1) is a potent immunosuppressive cytokine that promotes fibrosis by enhancing the synthesis of extracellular matrix components. The repair process following lung allograft injury is due to rejection or infection replaces lung parenchyma by fibrotic tissue, leading to pulmonary dysfunction. The role of TGF-b1 in this excessive healing process and increasing the risk of infection is unknown. Methods: We analysed our patient data to investigate the relevance of different factors on allograft fibrosis and its correlation with TGF-b1. Fibrosis was graded in H and E stained sections. TGF-b1 genotype was determined in all patients. Results: Patients were aged between 16 and 62 years (mean age of 39.6 years). Procedures were heart:lung (n32), double lung (n18), and SLT (n41). A total of 46 patients had lung allograft fibrosis diagnosed in transbronchial biopsies sections. Patients who had developed interstitial fibrosis had significantly more acute rejection episodes (mean 3.492.8) compared with patients without fibrosis (mean 2.192.2) (P0.024). The presence of eosinophils in the interstitium preceded and were associated with the development of fibrosis regardless of the rejection grade (P0.0001). TGF-b1 was heavily expressed in sections with fibrosis with a mean score of 6.892.9 compared with 2.490.6 in sections with no fibrosis (PB0.0001). TGF-b1 expression correlated positively with fibrosis grades (PB0.0001). The mean survival for patients with a fibrosis score \6 is 892.4973 days compared with mean survival 427978 in patients with scores B6 (P0.0001). Patients who developed fibrosis had homozygous TGF-b1 genotype that correlates with excessive TGF-b1 expressio