INSULIN-LIKE GROWTH FACTOR-I IS PARTIALLY RESPONSIBLE FOR FIBROBLAST PROLIFERATION INDUCED BY BRONCHOALVEOLAR LAVAGE FLUID FROM PATIENTS WITH SYSTEMIC-SCLEROSIS
Nk. Harrison et al., INSULIN-LIKE GROWTH FACTOR-I IS PARTIALLY RESPONSIBLE FOR FIBROBLAST PROLIFERATION INDUCED BY BRONCHOALVEOLAR LAVAGE FLUID FROM PATIENTS WITH SYSTEMIC-SCLEROSIS, Clinical science, 86(2), 1994, pp. 141-148
1. Interstitial lung disease is a common complication of systemic scle
rosis. 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 par
tially characterized the fibroblast proliferative activity of bronchoa
lveolar lavage fluid from 29 patients with systemic sclerosis, 19 with
and 10 without evidence of lung disease assessed by thin-section comp
uted tomography. 2. Bronchoalveolar lavage fluid from both groups of p
atients stimulated fibroblast proliferation compared with control subj
ects: systemic sclerosis with normal computed tomography, 27.7 (range
10.5-57.9)% above control; systemic sclerosis with abnormal computed t
omography, 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 antibo
dies to insulin-like growth factor-1 but not platelet-derived growth f
actor. 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 int
o 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 gr
owth 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 a
nd this contributes to the increased fibroblast-growth-promoting activ
ity of this fluid. The data also suggest that other mitogens are invol
ved, but we were unable to demonstrate a role for platelet-derived gro
wth factor.