Gamma tocopherol-enriched supplement reduces sputum eosinophilia and endotoxin-induced sputum neutrophilia in volunteers with asthma

Abstract

Background: We and others have shown that the gamma tocopherol (γT) isoform of vitamin E has multiple anti-inflammatory and antioxidant actions and that γT supplementation reduces eosinophilic and endotoxin (LPS)-induced neutrophilic airway inflammation in animal models and healthy human volunteers.

Objective: We sought to determine whether γT supplementation reduces eosinophilic airway inflammation and acute neutrophilic response to inhaled LPS challenge in volunteers with asthma.

Methods: Participants with mild asthma were enrolled in a double-blinded, placebo-controlled crossover study to assess the effect of 1200 mg of γT daily for 14 days on sputum eosinophils, mucins, and cytokines. We also assessed the effect on acute inflammatory response to inhaled LPS challenge following γT treatment, focusing on changes in sputum neutrophilia, mucins, and cytokines. Mucociliary clearance was measured using gamma scintigraphy.

Results: Fifteen subjects with mild asthma completed both arms of the study. Compared with placebo, γT notably reduced pre-LPS challenge sputum eosinophils and mucins, including mucin 5AC and reduced LPS-induced airway neutrophil recruitment 6 and 24 hours after challenge. Mucociliary clearance was slowed 4 hours postchallenge in the placebo group but not in the γT treatment group. Total sputum mucins (but not mucin 5AC) were reduced at 24 hours postchallenge during γT treatment compared with placebo.

Conclusions: When compared with placebo, γT supplementation for 14 days reduced inflammatory features of asthma, including sputum eosinophils and mucins, as well as acute airway response to inhaled LPS challenge. Larger scale clinical trials are needed to assess the efficacy of γT supplements as a complementary or steroid-sparing treatment for asthma.

Trial registration: ClinicalTrials.gov NCT02104505.

Keywords: Asthma; endotoxin; eosinophil; lipopolysaccharide; mucin; mucociliary clearance; neutrophil; tocopherol; vitamin E.

Conflict of interest statement

Conflicts of Interest: None.

Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1. Phase IIa crossover study design in volunteers with mild asthma (n=15)

Randomized, placebo controlled crossover study of γT supplement or safflower oil placebo in 15 subjects with mild asthma. Subjects were challenged with inhaled LPS followed 4 hours later by gamma scintigraphy to measure mucociliary clearance (MCC) and 6 hours later by sputum induction.

Figure 2. γT reduced post-treatment sputum eosinophils and mucins (n=13)

A) Sputum %eosinophils, B) sputum eosinophils/mg, C) total sputum mucins were reduced in post-treatment sputum samples during active treatment compared to placebo treatment.

Figure 3. γT attenuated LPS-induced sputum neutrophilia and mucin production (n=13)

A) Sputum %PMNs at 6-hours and B) 24-hours post-challenge were significantly reduced during active treatment compared to placebo. C) Total sputum mucins at 24-hours post-challenge were significantly reduced during active treatment compared to placebo.

Figure 4. γT was associated with attenuation of LPS-induced changes in MCC (n=15)

MCC is represented as mean retention versus time at post-treatment and 4-hours post-challenge for each treatment group. Inhaled LPS challenge resulted in significant slowing of MCC after placebo treatment, but no significant effect on MCC was seen after γT treatment.