Post-therapeutic change of cathelicidin LL-37 in asthmatics of different inflammatory phenotypes

Abstract

To explore the post-therapeutic change of cathelicidin LL-37 in asthmatics of different inflammatory phenotypes. Thirty-four patients with initially diagnosed asthma (asthma group) and 14 normal subjects (control group) were recruited at Nanfang Hospital from August 2009 to August 2010 for this prospective study. Sputum and venous blood samples were collected and analyzed for cell differential. Eosinophilic asthma was defined as the count of sputum eosinophils ≥ 3%. The LL-37 concentrations in plasma and sputum supernatant were measured by enzyme-linked immunosorbent assay (ELISA) kit. The subjects were treated with budesonide/formoterol (160/4.5 µg) one inhalation twice daily and re-examined after 1 month. Prior to treatment, there were no differences between the asthma and control groups in the levels of LL-37 in plasma and sputum supernatant (P = 0.427,0.427). The plasma concentrations of LL-37 in asthma group were negatively correlated with baseline forced expiratory volume in one second (FEV(1), r = -0.470, P = 0.005), percent predicted of FEV(1) (FEV(1)%pred, r = -0.421, P = 0.013) and forced vital capacity (FVC, r = -0.367, P = 0.033). After treatment, the plasma and sputum supernatant concentrations of LL-37 (M (Q(R))) in the asthma group (5.6 (16.2), 65.6 (184.0) µg/L) were significantly higher than those baseline concentrations (5.03 (9.21), 28.40(109.76) µg/L, P = 0.005, 0.015). In the eosinophilic asthma subgroup, the plasma and sputum supernatant concentrations of LL-37 (M (Q(R))) after treatment (5.3 (19.3), 65.6 (185.2) µg/L) were significantly higher than those baseline concentrations (6.7 (8.9) L, 35.3 (102.0) µg/L, P = 0.021,0.014). And in the non-eosinophilic asthma subgroup, the changes of plasma and sputum supernatant concentrations of LL-37 showed no significant differences (P = 0.139, 0.386). In the asthma group, the correlations between plasma concentrations of LL-37 and FEV(1), FEV(1)%pred, FVC were not statistically significant (P = 0.283, 0.706,0.272) after treatment. LL-37 may participate in the aggravation of asthma. The elevated concentrations of LL-37 in eosinophilic asthma is probably due to the resolved suppression of LL-37 expression by eosinophilic inflammation. But its mechanism needs further researches.