Cyclophosphamide combined with methylprednisolone ameliorates bleomycin-induced pulmonary fibrosis in rats through immunomodulatory mechanisms

Abstract

Background Idiopathic pulmonary fibrosis(IPF) is a distressing lung disorder with poor prognosis and high mortality rates.Immune factors are currently recognized as pathogenic agents throughout the onset of IPF.In clinical studies,the combination of methylprednisolone (MP) and cyclophosphamide (CTX) has great benefits for patients with IPF,but the immune mechanism of improving IPF is not clear. Results The lung inflammation and fibrosis model was established by intratracheal instillation of bleomycin (BLM).Pulmonary fibrosis was observed in rats on day 7 after BLM injection. With prolonged fibrosis,we can see that the expression of neutrophils and T lymphocytes was out of control.Our data suggests that immune disorders run through the whole process of pulmonary fibrosis both in the early stage(day 14)and in the advanced stage(day 28).The inflammation and immune disorders were better than before after intervention with medication. Conclusions The combination of MP and CTX can alleviate IPF by reducing inflammation,and improving T cell immunity.So CTX combined with MP can modulate immune disorders,which may be an effective anti-fibrosis drug in the treatment of clinical IPF patients.But we should pay attention to dosage and use course of the treatment,in order to prevent the occurrence of toxic side effects.