Title

In vitro supplementation with different tocopherol homologues can affect the function of immune cells in old mice

Abstract

Alpha-tocopherol (T) is the most common form of vitamin E in plasma and tissues. Alpha-T is also believed to be superior to its homologues β-T, γ-T, and δ-T in antioxidant activity. Biological activity of α-T has been intensively studied in a number of bodily systems. In contrast, the other homologues have received little attention beyond the evaluation of their relative antioxidant activity. We as well as others have previously shown that α-T can enhance cell-mediated immune function of aged animals and humans. Gamma-T is a principal form of vitamin E in the American diet and some cooking oils contain substantial amount of β-T and δ-T. Thus it is of public health interest to compare their biological effects with that of α-T in various systems. In this study, we used an in vitro supplementation protocol to determine immunologic effects of these T homologues on murine splenocytes. The results showed that all four T homologues enhance both spontaneous and mitogen-stimulated lymphocyte proliferation (LP) and the maximal enhancement produced by them was of the same magnitude. The dose range to produce maximal enhancement varied with different homologues. The efficiency was in the order of β-T ~ δ-T > γ-T > α-T. Interestingly, at 50 (optimal for α-T) and 150 μmol/L, while α-T enhanced LP, all the other homologues inhibited LP. This inhibition was found to be due to their cytotoxicity at these levels. T homologues had a differential effect on interleukin (IL)-2 and prostaglandin (PG)E2 production. IL-2 production by mouse splenocytes was not affected by α-T or β-T, but was increased by γ-T and δ-T. All T homologues, except for β-T, inhibited PGE2 production by mouse peritoneal macrophages. Cyclooxygenase activity, however, was inhibited by all T homologues. Analysis of cellular T showed that these T homologues were differentially incorporated into the cells in the order of β-T ~ δ-T > γ-T > α-T. Thus, all the T homologues enhance LP. However, the dose required to reach maximal enhancement varies among the homologues. On the other hand, they have a differential effect on IL-2 and PGE2 production. The difference in nature and magnitude of the effect on immune function does not correlate with their reported relative antioxidant activity and might be due to minor differences in their structure important to their other biological activities. Copyright (C) 2000 Elsevier Science Inc.

Publication Title

Free Radical Biology and Medicine

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