Relationship between serum zinc level and immunocompetence in protein-deficient and well-nourished weanling mice

Abstract

Two experiments were performed in which three-week-old male and female CBA/J mice were fed ad libitum for two weeks either a control diet (18.6% protein) containing adequate levels of all nutrients or a lowprotein diet (Experiment 1: 1.6%; Experiment 2: 0.6%) adequate in all other nutrients. Two thymus-dependent primary immune responses to sheep red blood cells (SRBC), viz. the antibody (hemagglutinin) response and the low-dose delayed hypersensitivity response, were tested in each experiment. Mice fed 1.6% protein maintained weaning weight, but exhibited low thymic and splenic indices (weight relative to body weight), low serum protein levels and low serum zinc levels. These animals, however, displayed normal immune responses to SRBC. Mice fed 0.6% protein lost about 15–20% of their initial (weaning) weight during the 14-day experiment, and exhibited low thymic and splenic indices, low serum protein levels and low serum zinc levels. Both the antibody response and the delayed hypersensitivity reaction were depressed in these animals. Subcutaneous zinc injections raised the serum zinc level to nearnormal in mice fed 0.6% protein, but did not influence either immune response examined. By contrast parenterally administered zinc reduced the antibody response of well nourished mice to about 15% of normal, although the delayed hypersensitivity response was not affected in this group of animals. A negative correlation (R=−0.72, P<0.02) was found between serum zinc level and hemagglutinin titer in the zinc-injected, well-nourished animals. The results suggest that thymus-dependent immune responses are highly resistant to the adverse effects of protein deficiency, but do not support the hypothesis (proposed by others) that secondary zinc deficiency is a primary underlying cause of the immunodepression which occurs in severe protein deficiency. In addition, it appears that zinc supplements can depress some immune responses of well-nourished individuals if the quantities administered overwhelm the mechanism(s) regulating serum zinc level.