Immunomodulatory effects of high-dose α-tocopherol acetate on mice subjected to sidestream cigarette smoke

Abstract

Several recent epidemiological investigations raise serious questions about the health effects of high-dose supplements of Vitamin E (VE) in cigarette smokers. To examine these findings, a total of 96 C57BL/6 mice were randomly assigned to eight groups in a 2×4 factorial design (smoke vs. sham smoke and normal diet vs. 3 VE supplements). The mice were exposed to sidestream cigarette smoke (SSCS), at 0.4 mg total particulate matter/m 3 air, from standard research cigarettes (1R4)/day or filtered room air at 30 min/day, 5 days/week, for 9 weeks through a nose-only exposure chamber. The American Institute of Nutrition 93G purified rodent diet was modulated with 75 (regular diet, 1-fold), 1050 (15-fold), 5550 (75-fold), and 11 175 (150-fold) IU dl-α-tocopherol acetate (α-TA)/kg as VE supplementation and provided ad libitum at an average intake rate of 4.11 g diet/mouse/day. This result demonstrated that SSCS exposure results in lung dysfunction, as indicated by a decrease of pulmonary dynamic compliance ( C dyn) and increase of lung resistance ( R L), and body weight loss in mice fed with regular diet. These changes accompanied with increases of bronchoalveolar lavage (BAL) concentrations of cytokines interleukin (IL)-1β, IL-4 and IFN-γ, as well as hepatic lipid peroxidation. However, supplemental α-TA at the doses of ⩾1050 IU/kg diet prevented the SSCS-induced body weight loss and lung dysfunction. α-TA at ⩾5550 IU/kg significantly increased BAL levels of IL-2 and IL-4 in both the sham SSCS and the SSCS groups. Given at 5550 IU α-TA/kg, but not higher, mice elevated BAL IL-1β level if they were exposed to SSCS. Hepatic lipid peroxidation was decreased in a dose-dependent fashion with different α-TA supplements in both the sham SSCS and SSCS groups. Neither SSCS nor α-TA had an effect on lung permeability, BAL IL-6, splenic T and B lymphocyte proliferation and their T helper (Th)1 and Th2 cytokines measured among all groups. Data suggest that supplemental α-TA may be needed to counteract SSCS-induced oxidative stress, but that potential side effects introduced by high dosage of this synthetic compound should be considered.