Prevention of the Immunodepressive Effects of Excess Dietary Leucine by Isoleucine and Valine in the Rat

Young adult male rats received for 5 weeks a balanced (18% casein) diet or a low protein (4% casein) diet. The latter was either unsupplemented or overloaded with L-leucine alone (7% dry diet weight) or with leucine (7%), isoleucine (0.20%) and valine (0.20%). One week before killing, the rats were immunized intraperitoneally against sheep red blood cells (SRBC) or against E. coli lipopolysaccharides (LPS). Excess leucine added to the low protein diet not only reduced ponderal growth and lymphopoiesis to a greater extent than did the same unsupplemented diet but also, contrary to the latter, significantly depressed the production of antibodies with complete disappearance of serum IgG globulins. The immunodepression concerned both thymus dependent (SRBC) and independent (LPS) immune responses. This contrasted with the previously reported exclusive impairment of thymus-dependent responses in rats subjected to protein deprived diets without amino acid imbalance. Since all the excess leucine-induced anomalies could be almost completely prevented by addition of small quantities of isoleucine and valine to the low protein diet, they apparently result from a secondary deficiency of the two latter branched chain amino acids due either to reduced intestinal absorption or rather to an excessive degradation of these leucine antagonists.