Infection is a major problem in the malnourished population. Increased host susceptibility has been attributed, at least in part, to defects in cell-mediated immunity. However, deficiencies in non-specific defense mechanisms, such as those mediated by interleukin-1 (IL-1) may be important in determining the outcome of infection. IL-1, a protein made by monocytes/macrophages and a number of other cells is responsible for initiating the febrile response, the outpouring of acute phase reactants, the fall in plasma trace metals, and other non-specific host defenses seen in infection. Previous studies suggest that IL-1 activity is diminished in both protein deficient animals and humans. Using the Fischer rat as a model, we propose to study the effects of protein malnutrition on IL-1 production. IL-1 activity will be assessed using a rat bioassay for the febrile response, plasma trace metal concentrations, and thymocyte proliferation. After establishing that defects in IL-1 infection will be studied in these animals. The febrile response, the fall in plasma iron and zinc, organ bacterial counts, and mortality rates, will be compared in protein-malnourished and well-nourished rats. The effect of IL-1 supplementation in improving the response to Salmonella infection will be studied using recombinant murine IL- 1. IL-1 supplementation, especially now that recombinant IL-1 is available, may have great potential for treating the infecting malnourished patient. However, some of the effects of IL-1 on muscle and amino acid metabolism may in fact be detrimental to the host. This study will attempt to establish the safety and efficacy of supplementing an infected host with IL-1.
| Bradley, S F; Kauffman, C A (1990) Aging and the response to Salmonella infection. Exp Gerontol 25:75-80 |
| Bradley, S F; Vibhagool, A; Fabrick, S et al. (1990) Monokine production by malnourished nursing home patients. Gerontology 36:165-70 |
| Bradley, S F; Vibhagool, A; Kunkel, S L et al. (1989) Monokine secretion in aging and protein malnutrition. J Leukoc Biol 45:510-4 |
| Bradley, S F; Kauffman, C A (1988) Effect of protein malnutrition on salmonellosis and fever. Infect Immun 56:1000-2 |
