The protective effects of methylprednisolone and cyclophosphamide against pulmonary fibrosis

AbstractBackground:In clinical studies, the combination of methylprednisolone (MP) and cyclophosphamide (CTX) has great benefits for patients with pulmonary fibrosis (PF), but the mechanism of improving PF is not clear.Methods:PF rat models were induced by bleomycin and treated with MP or MP/CTX combination. Transmission electron microscope, hematoxylin and eosin (H&E) and Masson staining were used to measure the morphology of PF. ELISA kits were used to test inflammatory factor levels. MDA, SOD, GSH-PX levels were determined using commercial kits. α-SMA and collagen I levels were examined by western blot and immunohistochemistry. T cells were analyzed with flow cytometry.Results:We found that the combined use of MP and CTX can reduce collagen deposition, α-SMA and collagen I levels in bleomycin induced PF. Moreover, combined treatment with MP and CTX decreased the levels of MDA and inflammatory factors (TNF-α, IL-1 β and IL-6), while increased the activities of SOD and GSH-PX. Further, MP and CTX combination changed T cell types in lung tissues, such as increasing CD4+CD25+Foxp3+cells.Conclusions:The combination of MP and CTX improved the degree of PF by reducing inflammation, oxidative stress and improving T cell immunity. These findings provide novel insights into the mechanisms by which MP and CTX combination affects PF.