IFN-gamma-inducible protein-10 attenuates bleomycin-induced pulmonary fibrosis via inhibition of angiogenesis

Few studies have addressed the importance of vascular remodeling in the lun g during the development of bleomycin-induced pulmonary fibrosis (BPF), For fibroplasia and deposition of extracellular matrix to occur, there must be a geometric increase in neovascularization, We hypothesized that net angio genesis during the pathogenesis of fibroplasia and deposition of extracellu lar matrix during BPF are dependent in part on a relative deficiency of the angiostatic CSC chemokine, IFN-gamma-inducible protein-10 (IP-10). To test this hypothesis, we measured IP-10 by specific ELISA in whole lung homogen ates in either bleomycin-treated or control mice and correlated these level s with lung hydroxyproline. We found that lung tissue from mice treated wit h bleomycin, compared with that from saline-treated controls, demonstrated a decrease in the presence of IP-10 that was correlated to a greater angiog enic response and total lung hydroxyproline content, Systemic administratio n of IP-10 significantly reduced BPF without any alteration in lung lymphoc yte or NK cell populations. This was also paralleled by a reduction in angi ogenesis. Furthermore, IP-10 had no direct effect on isolated pulmonary fib roblasts. These results demonstrate that the angiostatic CSC chemokine, IP- 10, inhibits fibroplasia and deposition of extracellular matrix by regulati ng angiogenesis.