Gamma Tocopherol (Gamma T) Supplementation Reduces Endotoxin-Induced Sputum Neutrophilia In Healthy Volunteers And Asthmatics Regardless Of Bmi Or Glutathione-S-Transferase Mu1 (Gstm1) Genotype

Through its unique antioxidant and anti-inflammatory properties, γT supplementation has shown benefit in reducing airway inflammation in preclinical and early-phase clinical studies. However, obesity increases systemic inflammation while the GSTM1 null genotype may alter host antioxidant defenses. This study, therefore, examines whether BMI and/or GSTM1 genotype modifies the response to inhaled endotoxin and/or the reduction of endotoxin-induced sputum neutrophilia following γT supplementation in healthy volunteers (HV) and asthmatics. Thirteen HV and 15 asthmatics underwent γT treatment followed by inhaled endotoxin challenge in two double-blind, placebo-controlled, cross-over studies. γT supplementation reduced post-challenge sputum neutrophilia compared to placebo in HV (p=0.03) and asthmatics (p=0.04). The effect of BMI and GSTM1 genotype on response to inhaled endotoxin and the reduction in endotoxin-induced sputum neutrophilia following γT treatment in each study was assessed using linear regression models and Wilcoxon Rank Sum Tests, respectively. BMI and GSTM1 genotype had no effect on response to inhaled endotoxin, as measured by increase in sputum neutrophils, in HV (p=0.17 and p=0.90, respectively) or asthmatics (p=0.81 and p=0.52, respectively). GSTM1 genotype had no effect on the reduction in endotoxin-induced sputum neutrophilia following γT treatment in HV (p=0.42) or asthmatics (p=0.78). Higher BMI was associated with greater reduction in post-challenge sputum neutrophilia following γT treatment in HV (p=0.03) but not in asthmatics (p=0.14). Response to inhaled endotoxin in HV and asthmatics is not affected by BMI or GSTM1 genotype. γT treatment reduces endotoxin-induced sputum neutrophilia regardless of BMI and GSTM1 genotype with enhanced responses seen in those with higher BMI.