Different angiogenic CXC chemokine levels in bronchoalveolar lavage fluid after interferon gamma-1b therapy in idiopathic pulmonary fibrosis patients

Background and aim: Pulmonary fibrosis is a devastating disease with few treatment options. Angiogenesis that leads to aberrant vascular remodeling is regulated by an opposing balance of angiogenic and angiostatic factors. The present study aims to evaluate the role of three angiogenic (IL-8, ENA-78 and GRO-a) and three angiostatic (MIG, IP-10, ITAC) chemokines in bronchoalveolar lavage fluid (BALF), before and after treatment with Interferon gamma-1b (IFN gamma-1b). Patients and methods: We studied prospectively 20 patients (16 males, 4 females) of median age 68 years (range, 40-75) with histologically confirmed IPF/UIP. Patients were assigned to receive IFN gamma-1b 200 mu g sc thrice a week. Angiogenic and angiostatic mediators' levels were measured by ELISA kits. Results: The levels of the angiogenic chemokines significantly decreased after 12 months (mo) of IFN-gamma-1b treatment (median values in pg/ml, IL-8/CXCL8: 640 vs. 81, p < 0.05, ENA-78/CXCL5: 191 vs. 51, p < 0.005 and GRO-alpha: 1827 vs. 710, p < 0.005). No significant differences were detected in the levels of the angiostatic chemokines after therapy (median values in pg/ml, IP-10/CXCL10: 56 vs. 56.5, p = 0.6, ITAC/CXCL11: 43 vs. 47, p = 0.11). However, a significant decrease in the MIG/CXCL9: 66 vs. 31, p = 0.006, has been detected. Conclusion: These findings support the notion that IFN gamma may be one of the important mediators regulating angiogenetic balance in IPF. However, IFN gamma-1b decreases MIG levels, finding that in association with no alteration in IP-10 and I-TAC levels, could explain in part the nonbeneficial effect of this drug in IPF. (C) 2008 Published by Elsevier Ltd.