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2000 ; 100
(4
): 487-93
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Vitamin E supplementation increases T helper 1 cytokine production in old mice
infected with influenza virus
#MMPMID10929076
Han SN
; Wu D
; Ha WK
; Beharka A
; Smith DE
; Bender BS
; Meydani SN
Immunology
2000[Aug]; 100
(4
): 487-93
PMID10929076
show ga
Compared with young mice, old mice infected with influenza virus have
significantly higher pulmonary viral titres, although these can be reduced
significantly with dietary vitamin E supplementation. T helper 1 (Th1) cytokines,
especially interferon-gamma (IFN-gamma), play an important role in defending
against influenza infection. However, there is an age-associated loss of Th1
cytokine production. Prostaglandin E2 (PGE2) 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 influenza severity in old mice, we studied the cytokine production
by splenocytes, and PGE2 production by macrophages (Mphi), in young and old C57BL
mice fed semipurified diets containing 30 (control) or 500 parts per million
(ppm) (supplemented) vitamin E for 8 weeks, and then infected with influenza
A/PC/1/73 (H3N2). Old mice fed the control diet had significantly higher viral
titres than young mice; old mice fed the vitamin 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 effect, respectively). Following
influenza infection, interleukin (IL)-2 and IFN-gamma production was
significantly lower in old mice than in young mice. Vitamin 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 lipopolysaccharide (LPS)-stimulated Mphi
PGE2 production than old mice fed the vitamin E diet or young mice fed either
diet. There was no significant age difference in IL-6, IL-1beta, or tumour
necrosis factor-alpha (TNF-alpha) production by splenocytes. Young mice fed the
vitamin E-supplemented diet had significantly lower IL-1beta (day 7) and
TNF-alpha production (day 5) compared with those fed the control diet. Old mice
fed the vitamin E-supplemented diet had significantly lower TNF-alpha production
(day 2) than those fed the control diet. Our results indicate that the vitamin
E-induced decrease in influenza viral titre is mediated through enhancement of
Th1 cytokines, which may be the result of reduced PGE2 production caused by
vitamin E.