Leukocyte Endogenous Mediator (LEM), an endogenous protein, has a central role in the initiation of a generalized system of host defenses during infection, inflammation and severe injury. The set of metabolic alterations induced by the synthesis and release of Leukocyte Endogenous Mediator involves a mobilization of amino acids from peripheral tissues to support enhanced protein synthesis in visceral tissues, a redistribution of trace minerals, the development of fever and an activation of nonspecific host defense. Recent experimental evidence in humans and laboratory animals has shown that certain aspects of this LEM-mediated host defense system are compromised by prior nutritional deprivation. Reduced synthesis or release of LEM during protein malnutrition has been suggested as the mechanism for the attenuated febrile response and relatve hyperferremia observed in infected animals that are protein-malnourished. Since protein-malnutrition is associated with an increased incidence and severity of bacterial infections, this proposal will investigate the relationship between protein-malnutrition, reduced capacity to synthesize or release LEM, altered nonspecific host-defense and increased mortality to infection and injury. Using a protein-malnourished guinea pig model, we will determine whether insufficient synthesis of LEM is responsible for the increased severity of infections and/or injury in the protein-malnourished animal and whether exogenous administration of partially-purified LEM in conjunction with dietary nutrients should be recommended as a therapy to improve host defense in protein-malnutrition.

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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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Surgery, Anesthesiology and Trauma Study Section (SAT)
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Beth Israel Deaconess Medical Center
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Qu, Z; Chow, J C; Ling, P R et al. (1997) Tissue-specific effects of chronic dietary protein restriction and gastrostomy on the insulin-like growth factor-I pathway in the liver and colon of adult rats. Metabolism 46:691-7
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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

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