ObjectiveTo explore the therapeutic effects of spleen aminopeptide on connective tissue disease-related interstitial lung disease (CTD-ILD) and its mechanism for anti-fibrosis. MethodsNinety patients with CTD-ILD admitted between February 2014 and May 2015 were recruited in the study. The CTD-ILD patients were randomly divided into group A (conventional therapy alone) and group B (conventional therapy plus spleen aminopeptide). Peripheral blood collected from CTD-ILD patients were subjected to performance of flow cytometric analysis and cytokine/chemokines profiling by liquid Chip and ELISA assay. Pulmonary function test and high resolution CT (HRCT) scan were performed before and after the treatments for 12 weeks. Human cytomegalovirus (HCMV) DNA in the patients' blood was tested by Q-PCR. ResultsSignificantly improved lung function and HRCT score were observed in group B, but not in group A. The levels of Treg and IFN-γ were significantly increased in group B, compared with those in group A where markedly increased IL-6, IL-10 and IL-17 were detected (P < 0.05). There was higher virus negative reversal rate in group B than that in group A (P < 0.05). ConclusionSpleen aminopeptid can effectively regulate deregulated immune microenvironment in CTD-ILD patients and inhibit HCMV replication, thereby block pulmonary fibrotic development.