Lymphocyte Glutathione Levels in Children With Cystic Fibrosis
Larry C. Lands, Vijaylaxmi Grey, Argyrios A. Smountas, Violeta G. Kramer and Danielle McKenna
Objective: Lung disease in cystic fibrosis (CF) is characterized by a neutrophilic inflammatory response. This can lead to the production of oxidants, and to oxidative stress in the lungs. Glutathione (GSH) represents the primary intracellular antioxidant, and provides an important defense in the epithelial lining fluid. Evidence suggests that lymphocyte GSH reflects lung GSH concentrations, and so could potentially serve as a peripheral marker of lung inflammation.
Methods: We assessed peripheral blood lymphocyte GSH concentrations in 20 children (13 boys) with CF who were in stable condition at the time of evaluation. Values were compared with nutritional status and lung function parameters.
Results: Patients were 11.7 6 3.03 years old (mean 6 SD). Their percentage of ideal body weight was 101.8 6 17.92%; FEV1, 79.5 6 19.22% predicted; FEV1/FVC, 75.0 6 10.08%; and residual volume (RV)/total lung capacity (TLC), 31.3 6 10.47%. For the group, the GSH concentration was 1.31 6 0.52 mmol/106 lymphocytes, which was not different from laboratory control values. GSH values were correlated with nutritional status (percentage of ideal body weight: r 5 0.49, p < 0.03) and the degree of gas trapping (RV/TLC: r 5 0.50, p < 0.03), and were correlated inversely with airflow limitation (FEV1, percent predicted: r 5 20.45, p < 0.05; FEV1/FVC: r 5 20.48, p < 0.04), but not with age, height, or weight (p > 0.1).
Conclusions: We interpret the inverse correlation between lymphocyte GSH concentration and lung function as a reflection of upregulation of GSH production by lung epithelial tissue in response to oxidative stress. We interpret the correlation between lymphocyte GSH concentration and nutritional status as a reflection of the role of cysteine in hepatic glutamine metabolism. Peripheral blood lymphocyte GSH concentration may potentially serve as a convenient marker of lung inflammation. Furthermore, the increased demand for GSH production in the face of ongoing inflammation suggests a potential role for supplementation with cysteine donors. (CHEST 1999; 116:201–205)
Key words: antioxidants; inflammation; oxidative stress Abbreviations: CF 5 cystic fibrosis; GSH 5 glutathione; GSSG 5 glutathione disulfide; rpm 5 revolutions per minute; SSA 5 5-sulphosalicylic acid; TLC 5 total lung capacity; TNF-a 5 tumor necrosis factor-a