Enteral vitamin E supplementation inhibits the cytokine response to endotoxin
E. M. Bulger, W. S. Helton, C. M. Clinton, R. P. Roque, I. Garcia and R. V. Maier
Department of Surgery, University of Washington, Seattle 98195, USA.
OBJECTIVE: To evaluate the effect of short-term, high-dose enteral
supplementation of 3 different vitamin E derivatives: free alpha-tocopherol
(VE), alpha-tocopherol succinate (VES), and alpha-tocopherol acetate (VEA)
on macrophage and monocyte activation. DESIGN: Sprague-Dawley rats (weight,
150-200 g) were assigned to 1 of 5 experimental groups: saline (control),
ethanol (control), VES (100 mg/kg), VEA (100 mg/kg), or VE (100 mg/kg).
Rats underwent oral gavage once per day for 5 days with 0.5 mL of their
assigned solution. All vitamin E derivatives were diluted in 75% ethanol.
Rats were then killed and whole-blood and peritoneal macrophages were
harvested and stimulated with lipopolysaccharide (10 microg/mL) in vitro.
Tumor necrosis factor (TNF) production was measured by enzyme-linked
immunosorbent assay. Additional serum samples were analyzed for
alpha-tocopherol concentration by high-performance lipid chromatography.
RESULTS: Whole-blood TNF production was maximal in the control groups after
3 hours of incubation and began to decline by 6 hours. Supplementation with
all 3 vitamin E derivatives resulted in suppression of
lipopolysaccharide-induced TNF production at both time points when compared
with both ethanol and saline controls (P<.05, analysis of variance
[ANOVA]). All 3 vitamin E derivatives also resulted in significant
inhibition of lipopolysaccharide-induced TNF production by peritoneal
macrophages when compared with their ethanol-carrier control but not with
the saline control (P<.05, ANOVA). The degree of TNF suppression
correlated directly with serum alpha-tocopherol levels. CONCLUSIONS: Our
data demonstrate that a short-term, high-dose enteral supplementation of
vitamin E can modulate the monocyte and macrophage response to endotoxin.
These data, along with other animal studies showing a protective effect of
vitamin E treatment in sepsis and ischemia-reperfusion injury, suggest a
potential role for vitamin E supplementation in patients at risk of the
systemic inflammatory response syndrome.