title: Immunomodulatory effects of high-dose alpha-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 x 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 11175 (150-fold) IU dl-alpha-tocopherol acetate (alpha-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)-1 beta, IL-4 and IFN-gamma, as well as hepatic lipid peroxidation. However, supplemental alpha-TA at the doses of > or = 1050 IU/kg diet prevented the SSCS-induced body weight loss and lung dysfunction. alpha-TA at > or = 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 alpha-TA/kg, but not higher, mice elevated BAL IL-1 beta level if they were exposed to SSCS. Hepatic lipid peroxidation was decreased in a dose-dependent fashion with different alpha-TA supplements in both the sham SSCS and SSCS groups. Neither SSCS nor alpha-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 alpha-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.
authors.affiliation: Center for Toxicology and Department of Pediatrics, University of Arizona, P.O. Box 245073, 1501 N. Campbell Avenue, Tucson, AZ 85724-5073, USA.
authors.forename: Shengjun
authors.initials: S
authors.lastname: Wang
authors.forename: Nina N
authors.initials: NN
authors.lastname: Sun
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.forename: Ronald R
authors.initials: RR
authors.lastname: Watson
authors.forename: Mark L
authors.initials: ML
authors.lastname: Witten
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D001835:Body Weight; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D019587:Dietary Supplements / Q000009:adverse effects; D005260:Female; D008054:Lipid Peroxides / Q000378:metabolism; D008099:Liver / Q000737:chemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010539:Permeability; D011897:Random Allocation; D012129:Respiratory Function Tests; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D024505:Tocopherols; D024502:alpha-Tocopherol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology*
chemical_list: D000276:Adjuvants, Immunologic; D000975:Antioxidants; D016207:Cytokines; D008054:Lipid Peroxides; D014028:Tobacco Smoke Pollution; D024502:alpha-Tocopherol; D024505:Tocopherols