摘要
Background The interleukin (IL)-32/tumor necrosis factor (TNF) a pathway is supposed to play a key role in the amplification of the immune response in chronic obstructive pulmonary disease (COPD) inflammation. Inhaled corticosteroids (ICS) in combination with long-acting I]2-agonists (LABA) have shown airway anti-inflammatory effects in recent studies, but the mechanism is still uncertain. Methods Patients were treated in a randomized, open-labeled, parallel group clinical trial with either a combination of salmeterol xinafoate/fluticasone propionate (SF; Seretide, GlaxoSmithKline) Diskus (50/500 pg twice daily) or ipratropium bromide/salbutamol (IS; Combivent, Boehringer Ingelheim) MDI (42 IJg/240 IJg quartic daily) for 12 weeks. At the start and the end of treatment, induced sputum was collected and the concentration of IL-32 and TNF-a, the number of neutrophUs and eosinophils were measured. Results Following 12 weeks of treatment, a statistically significant fall from baseline in the concentration of TNF-a in sputum (P=0.004) was seen after treatment with SF but not with IS. However, neither treatment had significant effects on the concentration of IL-32 in sputum. There was a decrease from baseline in the number of sputum neutrophils with SF that approached statistical significance (P=0.028) but not with IS, while the number of sputum eosinophils did not change significantly from baseline in either treatment group. There was a statistically significant decline from baseline in the quality of life as assessed by the St George's respiratory questionnaire in both the SF (P=0.004) and IS (P=0.030) treatment groups, but no evidence of improvement in lung function was observed in either group. Conclusion The sputum TNF-a and neutrophils, but not IL-32 and macrophages, could be reduced by ICS/LABA treatment, suggesting that IL-32 could be involved in the corticosteroid resistance of COPD inflammation.
Background The interleukin (IL)-32/tumor necrosis factor (TNF) a pathway is supposed to play a key role in the amplification of the immune response in chronic obstructive pulmonary disease (COPD) inflammation. Inhaled corticosteroids (ICS) in combination with long-acting I]2-agonists (LABA) have shown airway anti-inflammatory effects in recent studies, but the mechanism is still uncertain. Methods Patients were treated in a randomized, open-labeled, parallel group clinical trial with either a combination of salmeterol xinafoate/fluticasone propionate (SF; Seretide, GlaxoSmithKline) Diskus (50/500 pg twice daily) or ipratropium bromide/salbutamol (IS; Combivent, Boehringer Ingelheim) MDI (42 IJg/240 IJg quartic daily) for 12 weeks. At the start and the end of treatment, induced sputum was collected and the concentration of IL-32 and TNF-a, the number of neutrophUs and eosinophils were measured. Results Following 12 weeks of treatment, a statistically significant fall from baseline in the concentration of TNF-a in sputum (P=0.004) was seen after treatment with SF but not with IS. However, neither treatment had significant effects on the concentration of IL-32 in sputum. There was a decrease from baseline in the number of sputum neutrophils with SF that approached statistical significance (P=0.028) but not with IS, while the number of sputum eosinophils did not change significantly from baseline in either treatment group. There was a statistically significant decline from baseline in the quality of life as assessed by the St George's respiratory questionnaire in both the SF (P=0.004) and IS (P=0.030) treatment groups, but no evidence of improvement in lung function was observed in either group. Conclusion The sputum TNF-a and neutrophils, but not IL-32 and macrophages, could be reduced by ICS/LABA treatment, suggesting that IL-32 could be involved in the corticosteroid resistance of COPD inflammation.
基金
This study was supported by a grant from National Natural Science Foundation of China (No. 30770939).Acknowledgements: The authors acknowledge the support of the Spirometry Unit of Peking University Third Hospital for lung function tests.