Therapeutic Effects of Evasin-1, a Chemokine Binding Protein, in Bleomycin-Induced Pulmonary Fibrosis

CC chemokines play an important role in the pathogenesis of idiopathic pulmonary fibrosis. Few studies have evaluated the efficacy of therapeutically targeting CC chemokines and their receptors during interstitial lung diseases. In the present study, the therapeutic effects of Evasin-1, a tick-derived chemokine-binding protein that has high affinity for CCL3/microphage inflammatory protein (MIP)-1 alpha, was investigated in a murine model of bleomycin-induced lung fibrosis. CCL3/MIP-1 alpha concentrations in lung homogenates increased significantly with time after bleomycin challenge, and this was accompanied by increased number of leukocytes and elevated levels of CCL2/monocyte chemoattractant protein (MCP)-1, CCL5/regulated upon activation, normal T cell expressed and secreted, TNF-alpha and transforming growth factor-beta(1), and pulmonary fibrosis. Administration of evasin-1 on a preventive (from the day of bleomycin administration) or therapeutic (from Day 8 after bleomycin) schedule decreased number of leukocytes in the lung, reduced levels of TNF-alpha and transforming growth factor-beta(1), and attenuated lung fibrosis. These protective effects were similar to those observed in CCL3/MIP-1 alpha-deficient mice. In conclusion, targeting CCL3/MIP-1 alpha by treatment with evasin-1 is beneficial in the context of bleomycin-induced lung injury, even when treatment is started after the fibrogenic insult. Mechanistically, evasin-1 treatment was associated with decreased recruitment of leukocytes and production of fibrogenic cytokines. Modulation of CCL3/MIP-1 alpha function by evasin-1 could be useful for the treatment of idiopathic pulmonary fibrosis.