Effects Of BCG-PSN Combined With Glucocorticoid On Patients With Idiopathic Pulmonary Fibrosis

Objective:This study was designed to investigate the regulation of polysaccharide nucleic acid fraction of bacillus calmette guerin(BCG-PSN) for the peripheral blood mononuclear cells (PBMC) on patients with idiopathic pulmonary fibrosis and Th1/Th2 related cytokine secretion in blood.Compare with the effects of glucocoriticoid,prove that the combined therapeutic effect of the two was superior to using glucocorticoid alone and at the same time that could greatly reduce the impact of possible side effects resulted by glucocor- ticoid.Method:Thirty-two patients who have not been treated with glucocorticoids that meeting the inclusion criteriawere randomly divided into 2 groups:treatment group which was given the BCG-PSN combined with glucocorticoid(n=16) and the control group which was given glucocorticoid(n=16)alone.Give injections to the patients in accordance with the 0.5mg/(kg.d) of dexamethasone according to patients'weight,age and general state.After 2 or 3 months , according to the the growth of the disease of IPF patients that gradually begin to reduce, and then reduce to 0.125mg/(kg.d) as maintenance dose.Apply glucocorticoid to the patients of treatment group.At the same time,give intramuscular injection of polysaccharide nucleic acid fraction of bacillus calmette guerin(BCG-PSN) 2ml per time every other day.Stop giving the drug of BCG-PSN every other month.It will be finished in six month.Control group:Use glucocorticoid alone,give glucocorticoid to the patients of control group in accordance with the 0.5 mg/(kg.d) according to patients'weight,age and general state.The method of reducing the dose and the course of treatment are the same as the treatment group.Collect peripheral blood come from normal persons and patients before and after treatment in fasting state.Preserve plasma and 48-hour dedicated cell culture supernatants in the temperature of -20℃.Measure the level of IFN-γ, TGF-β,IL-4 in plasma and culture supernatants with ELISA Method.Use statistical methods when dealing with numerical value,observe the symptoms such as difficulty in breathing and cough,chest HRCT,lung function and evaluate the progress of patients'condition.Observe the differences between the two drugs on the pulmonary fibrosis in the occurrence and the development of inhibition.Rusult : Before treatment,there was no significant difference in the level of cytokines between the treatment group and the control group. After treatment ,the level of IFN-γin the treatment group increased(P<0.05),while the level of TGF-β,IL-4 decreased insignificantly (P<0.01). After treatment ,the level of the IL-4 in control group was significantly higher than normal people and pre-treatment patients (P<0.01),while the level of TGF-βdecreased significantly, (P<0.05);the level of the IFN-γwas not significant than before treatment.The comparison with healthy control group was not significant.Conclusion: (1) Com- bine BCG-PSN with glucocorticoid.To some extent,it can treat idiopathic pulm- onary fibrosis in clinical treatment.(2)BCG-PSN may play a two-way role of immune and regulation to IPF in the treatment,because BCG-PSN have the activation of induced lymphocyte proliferation.and it can promote the effect of the IFN-γ.Moreover,the increasing of the level of the IFN-γresulted that the level of the IL-4(Th2) decreased relatively. But the IPF patients with the treatment of glucocorticoid alone showed that the secretion of the IFN-γwas inhibited.The level of Th2 type cytokines such as IL-4 ,was significantly higher than the pre-treatment patients and healthy control group,and the cytokines TGF-βwhich has representative meaning from IPF patients also increased significantly.(3)The results showed that the level of IFN-γcan be increased by combining BCG-PSN with glucocorticoid,the level of IL-4 can be decreased, the increase of Th1/Th2 ratio suggested that the balance was transforming to the direction of Th2.(4)The combination of the two drug can not only improve the therapeutic effect of mild or moderate idiopathic pulmonary fibrosis,but aslo reduce the side effects of dexamethasone actively.But for the treatment of servere idiopathic pulmonary fibrosis,it had no significant effect.