Effects of Antioxidant Vitamins C, E, and β‐Carotene on Immune Functions in MRL/Ipr Mice and Rats

'The immune system recognizes, neutralizes, and eliminates viruses, foreign cells, and macromolecules. At the same time it is tolerant towards components of its own system. If the mechanisms of tolerance t o self antigens break down, autoant ibodies and autoantigen-specific T cells develop, and autoimmune diseases such a \ systemic lupus erythematosus (SLE) in humans can occur. In SLE or the lymphuproliferative disorder in MRL/lpr mice resembling SLE,' a central question is the origin of antibodies binding to a variety of self antigens. We propose that a t least one factor in the progress of autoimmune diseases is related to the oxidative modification of cellular structures by free radicals being continuously produced in the course of the normal aerobic metabolism. In addition, it is possible that these diseases develop rapidly in affected individuals because of genetic predispositions.' In these individuals, proteins a t the sites of aerobic metabolism would not be able to inactivate free radicals as effectively as in normal individuals. Accordingly, the progre\s of autoimmune diseases would partly depend on the concentrations of antioxidants at the critical sites, such as mitochondria and nuclear and plasma cell membranes. If the hypothesis is correct, slowing down the development of certain autoimmune diseases and consequently prolonging the life span in diseased animals should be possible by means of lowering the endogenous levels of free radicals using nutritional supplementation with antioxidants.