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

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.