Short-term Low-dose Theophylline Therapy In COPD Patients With The Effect Of Sputum Inflammatory Cells And Inflammatory Mediators IL-17,IL-8 And TNF-α

ObjectiveThis paper was foucs on pursue the anti-inflammatory effect and mechanism of short-term and low-dose theophylline therapy treat with stable COPD patients.Methods34 stable COPD patients were divided into two groups:theophylline group and placebo group randomized,12 twelve age-matched and healthy non-smokers were taken as control. COPD patients took theophylline sustained release tablets or placebo 100mg before breakfast and bedtime. The course of treatment was 12 weeks both of theophylline group and placebo group.The percentage of Neu/Leu and Mcp/Leu were recorded in induced sputum before and after treatment and the concentration of IL-17,IL-8 and TNF-a were detected in the sputum supernatant using enzyme linked immunosobent assay (ELISA).ResultsIn theophylline group, the Neu/Leu was higher pre-therapy than post-therapy [(89±4.14)%vs(83.4±6.98)%,P<0.05], the Mcp/Leu was lower in theophylline group pre-therapy than post-therapy[(6.4±4.11)%vs (12.3±6.96)%,P<0.05]. There were no significant change either Neu/Leu or Mφ/Leu in placebo group (all P>0.05) before and after treatment. Pre-and post-therapy the Neu/Leu and Mφ/Leu in theophylline group and placebo group were significantiy different with controls(all P<0.01).(2) Pre-and post-therapy sputum supernatant IL-17 levels of theophylline group [(49.5±10.35) pg/ ml, (39.1±8.78) pg/ml] and the placebo group [(42.8±8.94) pg/ml, (55.1±8.61) pg /ml] were significantly higher than the healthy control group [(31.6±6.04) pg/ml, all P<0.01]. After treatment the IL-17 level in theophylline group was significantly lower than pre-treatment theophylline group and the treated placebo group(all P<0.01). After treatment the IL-17 level in placebo group wad significantly higher than pre-treatment (P<0.01).(3) Pre-and post-therapy sputum supernatant TNF-a levels of theophylline group [(85.4±9.04) pg/ml,(73.4±13.48)pg/ml] and the placebo group [(80.5±9.66) pg/ml,(84.2±16.17)pg/ml]were significantly higher than the healthy control group [(56.9±12.81),allP<0.01]. After treatment the TNF-a level in theophylline group was significantly lower than before treatment theophylline group and the treated placebo group(all P＜0.05). The TNF-a level was no significant change before and after treatment in control (P>0.05). (4) Pre-and post-therapy sputum supernatant IL-8 levels of theophylline group [(174.4±61.11) pg/ml,(157.4±62.48) pg/ml] and the placebo group [(156.2±46.55) pg/ml,(187.6±60.94) pg/ml were significantly higher than the healthy control group[(54.12±16.38)pg/ml,all P＜0.01]. After treatment the IL-8 level in theophylline group was significantly lower compared to pre-treatment (P<0.05). After treatment the IL-8 level in placebo group wad significantly higher compared to pre-treatment.(P＜0.01). (5) The Neu/Leu was posotively correlated with the concentration of IL-17,IL-8 and TNF-αin the sputum supernatant(r=0.466,0.471,0.652 respextively, all P＜0.01). The Mcp/Leu was negatively correlated with the concentration of IL-17,IL-8 and TNF-a in the sputum supernatant(r=-0.44,-0.505,-0.686 respextively, all P<0.01).The FEV1% was negatively correlated with the concentration of IL-17,IL-8 and TNF-a in the sputum supernatant(r=-0.496,-0.516,-0.652 respextively, all P＜0.01). Sputum supernatants of TNF-αwas positively correlated with IL-17 and IL-8 (r=0.541,0.581 respextively,all P＜0.01)ConclusionSputum neutrophils and inflammatory mediators IL-17,IL-8 and TNF-αincrease in COPD, which participate in the process of airway inflammation. Sputum inflammatory mediators are associated with airflow limitation closely. Theophylline treatment can reduce the airway inflammatory cells and inflammatory mediators, which play an anti-inflammatory effect.