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.

Background: Aging is a natural process characterized by a progressive functional impairment and reduced capacity to respond adaptively to environmental stimuli.Idiopathic pulmonary fibrosis(IPF)has been found to increase considerably with age.Immunosenescence,oxidative stress,abnormal shortening of telomeres, apoptosis, and epigenetic changes affecting gene expression have been proposed to contribute to the aging process,and aging-associated diseases. The above indicates that aging can increase the incidence of IPF. So can the occurrence of aging be aggravated after IPF? We examined pathological damage, collagen deposition, oxidative stress and immunosenescence to determine whether bleomycin(BLM)-induced pulmonary fibrosis (PF) accelerates aging in rats. If so, what drugs can inhibit or delay this aging. In clinical studies,the combination of methylprednisolone(MP) and cyclophosphamide(CTX) has shown great benefits in patients with IPF, but its effect on aging resulting from fibrosis is not fully understood. Therefore, we investigated whether MP combined with CTX could delay or inhibit aging in IPF rats. It may provide new targets for the treatment of IPF. Methods: PF rat models were induced by BLM 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. α-SMA and collagen I levels were examined by western blot and immunohistochemistry. Malondialdehyde(MDA),myeloperoxidase(MPO),lutathione peroxidase(GSH-PX) and superoxide dismutase(SOD) levels were determined using commercial kits.T cells were analyzed with flow cytometry. Results: We found that pathological damage, collagen deposition, oxidative stress, and T-cell senescence were increased after BLM-induced PF. The combined use of MP and CTX can alleviate pathological damage, reduce oxidative stress response, such as reducing MDA and MPO levels, and increasing SOD and GSH-PX activities. And inhibition of T cell senescence in lung tissue, such as reduction of CD27-CD28- CD4+ T cells in BLM-induced PF. Conclusions: BLM-induced PF aggravated the occurrence of aging in rats. The combination of MP and CTX can inhibit or delay aging, and thus play a therapeutic role in IPF.These findings provide new insights into the mechanism by which MP and CTX act in combination on IPF.

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Background:Aging is a natural process characterized by a progressive functional impairment and reduced capacity to respond adaptively to environmental stimuli.Idiopathic pulmonary fibrosis(IPF)has been found to increase considerably with age.Immunosenescence,oxidative stress,abnormal shortening of telomeres, apoptosis, and epigenetic changes affecting gene expression have been proposed to contribute to the aging process,and aging-associated diseases.We used oxidative stress and immune senescence to identify the relationship between aging and pulmonary fibrosis(PF).In clinical studies,the combination of methylprednisolone(MP) and cyclophosphamide(CTX) has great benefits for patients with IPF,but the mechanisms involved in aging are not well understood. Methods:PF rat models were induced by bleomycin(BLM) 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.Malondialdehyde(MDA),myeloperoxidase(MPO),lutathione peroxidase(GSH-PX) and superoxide dismutase(SOD) levels were determined using commercial kits.T cells were analyzed with flow cytometry. Results: We found that the combined use of MP and CTX can reduce collagen deposition,decreased the level of MDA,while increased the level of MPO and the activities of SOD and GSH-PX.Further,MP and CTX combination inhibited T cell senescence in lung tissues, such as decreasing CD4+CD27-CD28-cells. Conclusions: Aging was associated with PF.The combination of MP and CTX improved the degree of PF by reducing oxidative stress and inhibiting T cell senescence.These findings provide novel insights into the mechanisms by which MP and CTX combination affects PF.

Background: 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.