Vitamin E supplementation increases T helper 1 cytokine production in old mice infected with influenza virus

Compared with young mice, old mice infected with influenza virus have signi ficantly higher pulmonary viral titres, although these can be reduced signi ficantly with dietary vitamin E supplementation. T helper 1 (Th1) cytokines , especially interferon-gamma (IFN-gamma), play an important role in defend ing against influenza infection. However, there is an age-associated loss o f Th1 cytokine production. Prostaglandin E-2 (PGE(2)) production, which inc reases with age, can modulate the T helper cell function by suppressing Th1 cytokine production To investigate the mechanism of vitamin E supplementat ion on reduction of influenza severity in old mice, we studied the cytokine production by splenocytes, and PGE(2) production by macrophages (M phi), i n young and old C57BL mice fed semipurified diets containing 30 (control) o r 500 parts per million (ppm) (supplemented) vitamin E for 8 weeks, and the n infected with influenza A/PC/1/73 (H3N2). Old mice fed the control diet h ad significantly higher viral titres than young mice; old mice fed the vita min E-supplemented diet had significantly lower pulmonary viral titres than those fed the control diet(P=0.02 and 0.001 for overall age and diet effec t, respectively). Following influenza infection, interleukin (IL)-2 and IFN -gamma production was significantly lower in old mice than in young mice. V itamin E supplementation increased production of IL-2 and IFN-gamma in old mice; higher IFN-gamma production was associated with lower pulmonary viral titre. Old mice fed the control diet showed significantly higher lipopolys accharide (LPS)-stimulated M phi PGE(2) production than old mice fed the vi tamin E diet or young mice fed either diet. There was no significant age di fference in IL-6, IL-1 beta, or tumour necrosis factor-alpha (TNF-alpha) pr oduction by splenocytes. Young mice fed the vitamin E-supplemented diet had significantly lower IL-1 beta (day 7) and TNF-alpha production (day 5) com pared with those fed the control diet. Old mice fed the Vitamin E-supplemen ted diet had significantly lower TNF-alpha production (day 2) than those fe d the control diet. Our results indicate that the vitamin E-induced decreas e in influenza viral titre is mediated through enhancement of Th1 cytokines , which may be the result of reduced PGE(2) production caused by Vitamin E.