Insulinlike growth factor-1 in lung transplants with obliterative bronchiolitis

Bronchiolitis obliterans syndrome (BOS) is the major complication limiting survival of lung transplant recipients (Tx patients). The mechanisms underl ying this fibrotic process are not known. We assessed IGF-1 and IGFBP-3 exp ression, critical mediators in different models of pulmonary fibrosis, in n ine Tx patients. Three of them developed a BOS at 8, 14, and 17 mo postgraf t, respectively. Two of the remaining six displayed a recurrent cytomegalov irus (CMV) infection, and four are in stable condition. IGF-1 mRNA expressi on was quantitated by RT-PCR in cells from four to six BAL per patient perf ormed during the first 6 mo postgraft. Contrasting with a constantly low ex pression of IGF-1 mRNA in BAL cells from the six patients without BOS, the three patients with BOS presented marked peaks of IGF-1 on two to five occa sions during the study period. These peaks, 3- to 13-fold increased compare d with values from the former patients, preceded the diagnosis of BOS by 7, 13, and 17 mo, respectively. On the other hand, IGFBP-3 was highly and exc lusively expressed in the three patients with BOS, the mRNA as well as the gene product as demonstrated by Western blotting. Our data strongly argue f or a role of IGF-1 and IGFBP-3 in the fibrotic process underlying BOS, and for their possible value as an early marker of this complication.