INSULIN-LIKE GROWTH FACTOR-I IS PARTIALLY RESPONSIBLE FOR FIBROBLAST PROLIFERATION INDUCED BY BRONCHOALVEOLAR LAVAGE FLUID FROM PATIENTS WITH SYSTEMIC-SCLEROSIS

1. Interstitial lung disease is a common complication of systemic sclerosis. The mechanism by which excess collagen is deposited in the lung is poorly understood, but is thought to involve release of mediators which activate lung fibroblasts. In this study we investigated and partially characterized the fibroblast proliferative activity of bronchoalveolar lavage fluid from 29 patients with systemic sclerosis, 19 with and 10 without evidence of lung disease assessed by thin-section computed tomography. 2. Bronchoalveolar lavage fluid from both groups of patients stimulated fibroblast proliferation compared with control subjects: systemic sclerosis with normal computed tomography, 27.7 (range 10.5-57.9)% above control; systemic sclerosis with abnormal computed tomography, 26.7 (range 5.0-47.8)% above control, P<0.02 in both cases. 3. The activity was reduced by about one-third by neutralizing antibodies to insulin-like growth factor-1 but not platelet-derived growth factor. Levels of insulin-like growth factor-1 of bronchoalveolar fluid were increased in patients with systemic sclerosis [2.10 (range 1.10-3.48)ng/ml of bronchoalveolar lavage fluid] compared with controls [1.45 (range 1.10-2.05) ng/ml; P<0.01]. When patients were subdivided into those with abnormal computed tomography [2.10 (range 1.20-3.48)ng/ml] and those with normal computed tomography [1.85 (range 1.10-2.90) ng/ml] only the values for the group with evidence of lung disease were increased compared with control subjects (P<0.02). Platelet-derived growth factor could not be detected in bronchoalveolar lavage fluid from any group. Fractionation of bronchoalveolar lavage fluid demonstrated activity in several fractions consistent with the molecular masses of insulin-like growth factor-1 associated with binding proteins. 4. We conclude that bronchoalveolar lavage fluid from patients with systemic sclerosis contains increased levels of insulin-like growth factor-1 and this contributes to the increased fibroblast-growth-promoting activity of this fluid. The data also suggest that other mitogens are involved, but we were unable to demonstrate a role for platelet-derived growth factor.