| Pulmonary fibrosis is a chronic inflammatory lung disease that is characterized histopathologically by the presence of usual interstitial pneumonia. The prevalence rate of pulmonary fibrosis increased with age, and it has a Five-Year survival rate under 30% after diagnosis. There are no effective therapeutic strategies to this disease till now. The approach in the medical treatment of pulmonary fibrosis is merely adequate, so the discovery of anti-fibrosis drug is extremely urgent. The immune regulation plays an important role in the development of pulmonary fibrosis, and there is a Th2-dominant microenvironment in the advanced stage of this disease with limited Thl-type immune responses which has stimulant and protective effect. In our opinion the strategy to treat pulmonary fibrosis is breaking the immune suppress induced by Th2-type immune responses and more importantly is reserving moderate Thl-type immune responses. This theory also illustrated why the anti-inflammation drug has less effect on pulmonary fibrosis. Allergic diseases also were regulated by the immune response and allergic cells. It has been confirmed that Th2-type immune responses created by mast cell, eosinophil and basophil, can participate the development of allergy by inducing immune suppress, however, Thl-type immune responses can down regulate the immune suppress. Due to these phenomena and the allergic cells have closely associated with pulmonary fibrosis, we gave a hypothesis that using an anti-allergy drug can attenuate pulmonary fibrosis by regulation of the immune responses. In the first review, we summarize the general overview of pulmonary fibrosis include of pathogenesis, diagnosis principle, treatment and the medicine used to treat this disease in clinic as well as in clinical trials. In second review, we summarize the relationship between allergy and fibrosis include of asthma and fibrosis, the role of eosinophil, basophil and mast cell in pulmonary fibrosis. Based on previous theory, we chose Rupatadine as candidate drug to treat pulmonary fibrosis, it is a new generation dual inhibitor of H1 and PAF receptors used to treat allergies, which had been discovered by Uriach and launched in 2003 in Span. Previous pharmacology studies have shown that, Rupatadine can inhibit the degranulation of mast cells and the release of biochemical mediators from allergic cells. We used bleomycin-induced mice pulmonary fibrosis model and SiO2 induced silicosis model to test the hypothesis that Rupatadine may attenuate this chronic lung disease through its immune modulation property. Meanwhile, we compared the anti-fibrosis effects of Rupatadine with Histamine H1 receptor antagonist loratadine and PAF receptor antagonist CV-3988 at same dosage. Our results demonstrated that treatment with Rupatadine attenuated bleomycin-induced pulmonary fibrosis, reduced the mortality of fibrosis mouse, ameliorated the inflammatory responses, reversed the immunosuppressive Th2-dominant microenvironment, reserved a moderate Thl-type immune response in fibrosis mice and inhibited Epithelial-mesenchymal transition after bleomycin-instilled, in addition, rupatadine can reverse the M2 polarization to M1 after bleomycin injured. We found that single usage of Loratadine or CV-3988 had fewer effects of anti-inflammation and anti-fibrosis compared with rupatadine. We also demonstrated the anti-fibrosis effect of rupatadine on SiO2 induced silicosis model. So we have the conclusion that, rupatadine is a useful drug against pulmonary fibrosis with good safety. It can attenuate fibrosis through its immune regulation effect and this finding provides directive significance for clinical therapy.
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