Free Radical Theory of Aging: Effect of Free‐Radical‐Reaction Inhibitors on the Immune Response†

Abstract

Immune responses decline with age. Endogenous free radical reactions, implicated in aging, may contribute to this decline. To evaluate this possibility, either α‐tocopherol acetate (vitamin E) or a quinoline derivative (Santoquin), both free‐radical‐reaction inhibitors, were added to the diet of C3HeB/FeJ female mice from age 6 weeks through 88 weeks at a level of 0.25 percent by weight of the diet. Both these antioxidants enhanced immune responses up to age 88 weeks, and probably also for the remainder of the lifespan; the experiment was stopped at age 88 weeks, as all the mice had been used for assay. Vitamin E had a greater effect than Santoquin on humoral responses, whereas cell‐mediated responses were enhanced more by Santoquin. Prompted by the foregoing study, levamisole or one of a number of different free radical inhibitors was added to the diet of groups of young mice for one month, after which the humoral response of spleen cells were determined. The five free radical inhibitors found to be as effective as levamisole were: 2‐mercaptoethanol, butylated hydroxytoluene, 2‐mercaptoethylamine, Santoquin, and sodium hypophosphite. These studies suggest, but do not prove, that some endogenous free radical reactions contribute to the decline of the immune response with age. This decline can be ameliorated by adding inhibitors of free radical reactions to the diet.

Effect of Santoquin on humoral immune function in mice: lack of interference with selenium utilization

“…This appears to contradict earlier studies suggesting that enhanced immune function was the basis for increased longevity in mice given Santoquin at this same level (7,8). We report here these results together with studies aimed at exploring possible modes for this suppression of immune function.…”

Life Span Studies in <i>Zaprionus paravittiger</i>with Sodium Hypophosphite Feeding

“…This application was grad ually abandoned and SHP became an ingre dient of tonics. The latter use was fortified with the realization of the antioxidative property of SHP [6,23,24], Its use as freeradical scavenger in living systems and the subsequent effect on ageing has been studied in relation to immune response only by Har man et al [11] and Hannan [12]. Aforesaid reports motivated the use of SHP as an an tioxidant in the present investigation.…”

The aging process.

“…Humoral and cell-mediated immune responses are enhanced by adding antioxidants to the diet of mice (51). Santoquin and 2-mercaptoethylamine were particularly effective; addition of 0.25% Santoquin or 0.5% 2-mercaptoethylamine increased the humoral response of female C3HB/FeJ mice spleen cells by 94% and 79%, respectively.…”