Characteristics Of Eosinophil And Neutrophil Inflammatory Mediators In Aging Asthma Subjects

Abstract

RATIONALE: We have previously shown differences in eosinophil effector functions in vitro and sputum neutrophil levels in young and aging asthma subjects. We sought to characterize eosinophil and neutrophil inflammatory mediators involved in the pathogenesis of asthma, in young and aging asthma subjects at baseline disease.METHODS: Human subjects with mild to moderate asthma between the ages of 20-40 (younger) and 50-70 (aging) were recruited. Baseline characterizations of lung function and sputum analysis were performed. Purified eosinophils and neutrophils stimulated with calcium ionophore were evaluated by ELISA for leukotriene C4 (LTC4), eosinophil derived neurotoxin (EDN), and leukotriene B4 (LTB4) production. The sputum was analyzed for cysteinyl leukotrienes, LTB4, EDN, and neutrophil elastase (NE) levels.RESULTS: Sputum analysis revealed no difference in the percentage of eosinophils between both age groups but a trend (p = 0.08) towards a higher percentage of neutrophils in aging asthma subjects was found. In vitro LTC4, EDN, and LTB4 production in calcium ionophore stimulated eosinophils and neutrophils were comparable in both age groups. Sputum analysis revealed no differences in EDN or cysteinyl leukotriene production. However, there was a trend (p = 0.10) for higher NE levels and significantly lower levels (p = 0.05) of LTB4 in the sputum of aging asthma subjects.CONCLUSIONS: Eosinophils and neutrophils in aging asthma subjects are capable of comparable leukotriene production in vitro. Despite a higher percentage of sputum neutrophils in aging asthma subjects, a decreased level of LTB4 and increased level of NE was found in vivo suggesting that specific age-related regulation of neutrophil function is occurring in the airway. RATIONALE: We have previously shown differences in eosinophil effector functions in vitro and sputum neutrophil levels in young and aging asthma subjects. We sought to characterize eosinophil and neutrophil inflammatory mediators involved in the pathogenesis of asthma, in young and aging asthma subjects at baseline disease. METHODS: Human subjects with mild to moderate asthma between the ages of 20-40 (younger) and 50-70 (aging) were recruited. Baseline characterizations of lung function and sputum analysis were performed. Purified eosinophils and neutrophils stimulated with calcium ionophore were evaluated by ELISA for leukotriene C4 (LTC4), eosinophil derived neurotoxin (EDN), and leukotriene B4 (LTB4) production. The sputum was analyzed for cysteinyl leukotrienes, LTB4, EDN, and neutrophil elastase (NE) levels. RESULTS: Sputum analysis revealed no difference in the percentage of eosinophils between both age groups but a trend (p = 0.08) towards a higher percentage of neutrophils in aging asthma subjects was found. In vitro LTC4, EDN, and LTB4 production in calcium ionophore stimulated eosinophils and neutrophils were comparable in both age groups. Sputum analysis revealed no differences in EDN or cysteinyl leukotriene production. However, there was a trend (p = 0.10) for higher NE levels and significantly lower levels (p = 0.05) of LTB4 in the sputum of aging asthma subjects. CONCLUSIONS: Eosinophils and neutrophils in aging asthma subjects are capable of comparable leukotriene production in vitro. Despite a higher percentage of sputum neutrophils in aging asthma subjects, a decreased level of LTB4 and increased level of NE was found in vivo suggesting that specific age-related regulation of neutrophil function is occurring in the airway.