Induction of Thymic Dysfunction by Protein Malnutrition

Stevenson, John

Abstract

Protein malnutrition is one of the most serious widespread health problems today. Complications of child development during protein malnutrition include poor immune system development and depressed host resistance to infection. Studies in my laboratory have shown that protein malnourished weanling mice develop an immunodeficiency syndrome characterized by impeded body weight gain, depressed growth of the thymus and spleen, and delayed or depressed development of immune responsiveness. The features of this syndrome suggest that it involves thymic dysfunction, which causes reduced splenic T lymphocyte responsiveness. T lymphocytes play a pivotal role in induction and maintenance of the immune responses necessary for prevention of infection and for recovery from infectious disease. If its infectious disease consequences are to be avoided, and if the people who have protein malnutrition are to be restored to good health, it is important to understand the mechanisms that cause this immunodeficiency syndrome. The proposed research will elucidate mechanisms of induction and maintenance of this protein malnutrition induced immunodeficiency syndrome. The roles of elevated corticosterone, depressed zinc, and depressed albumin levels in the plasma of mice that develop this syndrome will be investigated. First, temporal changes in the levels of corticosterone, zinc, and albumin in the plasma of weanling mice fed a protein deficient diet will be quantified and compared with those of mice fed a protein sufficient diet. Second, repletion and depletion experiments will be performed to assess the relevance to depressed or delayed development of mitogen responsiveness of abnormal levels of these factors. These experiment will also provide insight into the mechanisms that underlie the changes in these factors and the development of the immunodeficiency syndrome. The results of this research will provide insight into the roles of elevated corticosterone, depressed zinc, and depressed albumin levels in plasma in induction and maintenance of the protein malnutrition induced immunodeficiency syndrome. They will also provide the basis for generation of a model to explain the quantitative contributions of these factors in the development of this syndrome and explains how they act synergistically to accomplish this.