SUMMARYCompared with young mice, old mice infected with in¯uenza virus have signi®cantly higher pulmonary viral titres, although these can be reduced signi®cantly with dietary vitamin E supplementation. T helper 1 (Th1) cytokines, especially interferon-c (IFN-c), play an important role in defending against in¯uenza infection. However, there is an age-associated loss of Th1 cytokine production. Prostaglandin E 2 (PGE 2 ) production, which increases with age, can modulate the T helper cell function by suppressing Th1 cytokine production. To investigate the mechanism of vitamin E supplementation on reduction of in¯uenza severity in old mice, we studied the cytokine production by splenocytes, and PGE 2 production by macrophages (Mw), in young and old C57BL mice fed semipuri®ed diets containing 30 (control) or 500 parts per million (ppm) (supplemented) vitamin E for 8 weeks, and then infected with in¯uenza A/PC/1/73 (H3N2). Old mice fed the control diet had signi®cantly higher viral titres than young mice; old mice fed the vitamin E-supplemented diet had signi®cantly lower pulmonary viral titres than those fed the control diet (P=0 . 02 and 0 . 001 for overall age and diet effect, respectively). Following in¯uenza infection, interleukin (IL)-2 and IFN-c production was signi®cantly lower in old mice than in young mice. Vitamin E supplementation increased production of IL-2 and IFN-c in old mice; higher IFN-c production was associated with lower pulmonary viral titre. Old mice fed the control diet showed signi®cantly higher lipopolysaccharide (LPS)-stimulated Mw PGE 2 production than old mice fed the vitamin E diet or young mice fed either diet. There was no signi®cant age difference in IL-6, IL-1b, or tumour necrosis factor-a (TNF-a) production by splenocytes. Young mice fed the vitamin E-supplemented diet had signi®cantly lower IL-1b (day 7) and TNF-a production (day 5) compared with those fed the control diet. Old mice fed the vitamin E-supplemented diet had signi®cantly lower TNF-a production (day 2) than those fed the control diet. Our results indicate that the vitamin E-induced decrease in in¯uenza viral titre is mediated through enhancement of Th1 cytokines, which may be the result of reduced PGE 2 production caused by vitamin E.