Expression of insulin-like growth factor-I (IGF-I) in alveolar macrophages and lymphocytes obtained by bronchoalveolar lavage (BAL) in interstitial lung diseases (ILD). Assessment of IGF-I as a potential local mitogen and antiapoptotic cytokine.

Little is known about IGF-I expression in the alveolar lymphocytes (AL), and about local role of IGF-I in phy- siological conditions and in interstitial lung diseases. Bronchoalveolar lavage was carried out in patients with silicosis, asbestosis, idiopathic pulmonary fibrosis (IPF) and sarcoidosis, as well as in control subjects (n=13, 9, 12, 56, 15, resp). Alveolar macrophages (AM) and lymphocytes (AL) were studied for (1) IGF-I, BCL-2, Fas and Fas Ligand expression and (2) cell cycle (incl. sub-G 1 peak of late apoptosis) with propidium iodide (PI). Flow cytometry (FC) and immunocyto- chemistry were used. AL early apoptosis was detected by Annexin V FITC/PI staining. IGF-I was present in AL of all test- ed groups. The number of IGF-I positive AL was significantly higher in IPF (52 ± 6.7%) and in later (II and III) stages of sarcoidosis (39 ± 7.8 vs 16 ± 4.0% in controls, p<0.05). Increased BCL-2 expression in AL was detected in IPF and sar- coidosis. In all tested groups, AL were almost exclusively Fas+ T cells. Generally, a low number of AL entered apoptosis; no significant differences were found between patient groups, except decreased apoptosis rate in sarcoidosis (0.60 ± 0.17 vs 1.15 ± 0.33% in controls, p<0.05). Proportion of AL positive for IGF-I was significantly correlated with parameters reflect- ing AL and AM cell proliferation and BCL-2 expression (e.g. AL IGF-I+ vs AM in S phase of cell cycle: r s = +0.50, p=0.001), but not with apoptosis. The results show that human alveolar lymphocytes express IGF-I in normal conditions, as well as in ILD. The proportion of IGF-I+ lymphocytes was significantly increased in IPF and at later stages of sarcoidosis. In our material there was no evidence for profibrogenic or antiapoptotic activity of IGF-I. We suggest that IGF-I originat- ing from AL may be locally active as a mitogen for alveolar macrophages and lymphocytes in ILD.