Lymphocyte glutathione levels in children with cystic fibrosis

Objective: Lung disease in cystic fibrosis (CF) is characterized by a neutr ophilic inflammatory response. This can lead to the production of oxidants, and to oxidative stress in the lungs. Glutathione (GSH) represents the pri mary intracellular antioxidant, and provides an important defense in the ep ithelial lining fluid. Evidence suggests that lymphocyte GSH reflects lung GSH concentrations, and so could potentially serve as a peripheral marker o f lung inflammation. Methods: We assessed peripheral blood lymphocyte GSH concentrations in 20 c hildren (13 boys) with CF who were in stable condition at the time of evalu ation. Values were compared with nutritional status and lung function param eters. Results: Patients were 11.7 +/- 3.03 years old (mean +/- SD). Their percent age of ideal body weight was 101.8 +/- 17.92%; FEV1, 79.5 +/- 19.22% predic ted; FEV1/FVC, 75.0 +/- 10.08%; and residual volume (RV)/total lung capacit y (TLC), 31.3 +/- 10.47%. For the group, the GSH concentration was 1.31 +/- 0.52 mu mo/10(6) lymphocytes, which was not different from laboratory cont rol values. GSH values were correlated with nutritional status (percentage of ideal body weight: r = 0.49, p < 0.03) and the degree of gas trapping (R V/TLC: r = 0.50, p < 0.03), and were correlated inversely with airflow limi tation (FEV1, percent predicted: r = -0.45, p < 0.05; FEV1/FVC: r = -0.48 i s, p < 0.04), but not with age, height, or weight (p > 0.1). Conclusions: We interpret the inverse correlation between lymphocyte GSH co ncentration and lung function as a reflection of upregulation of GSH produc tion by lung epithelial tissue in response to oxidative stress. We interpre t the correlation between lymphocyte GSH concentration and nutritional stat us as a reflection of the role of cysteine in hepatic glutamine metabolism. Peripheral blood lymphocyte GSH concentration may potentially serve as a c onvenient marker of lung inflammation. Furthermore, the increased demand fo r GSH production in the face of ongoing inflammation suggests a potential r ole for supplementation with cysteine donors.