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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK041128-02
Application #
3241782
Study Section
Metabolic Pathology Study Section (MEP)
Project Start
1988-12-01
Project End
1993-11-30
Budget Start
1989-12-01
Budget End
1990-11-30
Support Year
2
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02215
Sabbatini, Maria E; Chen, Xuequn; Ernst, Stephen A et al. (2008) Rap1 activation plays a regulatory role in pancreatic amylase secretion. J Biol Chem 283:23884-94
Qu, Z; Ling, P R; Tahan, S R et al. (1996) Protein and lipid refeeding changes protein metabolism and colonic but not small intestinal morphology in protein-depleted rats. J Nutr 126:906-12
Ling, P R; Gollaher, C; Colon, E et al. (1995) IGF-I alters energy expenditure and protein metabolism during parenteral feeding in rats. Am J Clin Nutr 61:116-20
Tahan, S R; Wei, Y; Ling, P et al. (1995) Influence of formalin fixation time and tissue processing method on immunoreactivity of monoclonal antibody PC10 for proliferating cell nuclear antigen. Mod Pathol 8:177-82
Sierra, P; Ling, P R; Istfan, N W et al. (1995) Fish oil feeding improves muscle glucose uptake in tumor necrosis factor-treated rats. Metabolism 44:1365-70
Ling, P R; Istfan, N W; Colon, E et al. (1995) Differential effects of interleukin-1 receptor antagonist in cytokine- and endotoxin-treated rats. Am J Physiol 268:E255-61
Wan, J M; Istfan, N W; Ye, S L et al. (1995) Insulin-like growth factor-1 is not mitogenic for the Walker-256 carcinosarcoma. Life Sci 56:747-56
Wan, J M; Bistrian, B R; Figoni, M A et al. (1994) Influence of interleukin-2 infusion on cell cycle kinetics in the Walker-256 carcinosarcoma. J Leukoc Biol 55:241-7
Wan, J M; Fogt, F; Bistrian, B R et al. (1993) Evaluation of antitumor effect of tumor necrosis factor in terms of protein metabolism and cell cycle kinetics. Am J Physiol 265:C365-74
Ling, P R; Istfan, N; Colon, E et al. (1993) Effect of fish oil on glucose metabolism in the interleukin-1 alpha-treated rat. Metabolism 42:81-5

Showing the most recent 10 out of 15 publications