Fever and weight loss, often accompanied by diarrhea, form a common symptom complex developing in the course of AIDS. (Group IV. Subgroup A. Constitutional Disease and Subgroup C. Secondary Infectious Disease). Two hypotheses for this occurrence that are not mutually exclusive seem reasonable and worthy of investigation. The monokines, interleukin-1 (IL- 1) and tumor necrosis factor (TNF), which have been shown to mimic virtually every aspect of the metabolic response to infection, may be responsible. Their chronic release might be attributed to human immunodeficiency virus infection of IL-1, or TNF-secreting cells or to infection by one of twelve specified infectious diseases listed in the surveillance definition of AIDS by the CDC. We have demonstrated that the acute administration of biologically derived IL-1, human recombinant Il-1 and TNF, and the combination of the latter to experimental animals have effects on whole body energy metabolism, whole body and individual tissue protein kinetics, fat and glucose metabolism, and, most recently, gastric emptying. We have also shown that some of these changes (fever and leucine oxidation in response to IL-1, shock and metabolic acidosis in response to TNF) are blunted or prevented when animals are prefed with fish oil. The presumed mechanism is the competitive inhibition of omega 3 fats on arachidonic acid metabolism to prostanoids.
The aims of this proposal are to define the effects on protein, carbohydrate and energy metabolism of chronic recombinant monokine administration either intermittently or continuously in the rat model, to determine the acute and chronic effects of recombinant monokine administration on gastric emptying and intestinal motility, to explore whether pretreatment with a fish oil-based diet rich in omega 3 fats can alter the metabolic and gastrointestinal responses to chronic recombinant infusion determined above, and, in an exploratory manner, to determine if animals chronically receiving recombinant monokines are more susceptible to small bowel colonization and diarrhea.
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