ALTERED MACROPHAGE INTRACELLULAR SIGNALING INDUCED BY PROTEIN-CALORIEMALNUTRITION

Protein-calorie malnutrition (PCM) contributes to increased morbidity and mortality through impairment of host defense mechanisms and reduce d macrophage function. The present study examined alterations in macro phage intracellular signaling associated with the impairment in host d efense capabilities. Mice were randomized to either control (regular d iet) or protein-free diets (PCM) and pair-fed for 1 week. Following en dotoxin stimulation, peritoneal macrophages from PCM. mice produce sig nificantly less TNF-alpha and IL-6 product and had significantly less cell-associated IL-6 when compared to macrophages from control mice. S imilarly, macrophages from PCM mice had a significant reduction in mRN A levels for both TNF-alpha and IL-6. Other macrophage intracellular s ignaling mechanisms, such as calcium flux and tyrosine kinase phosphor ylation were also altered by PCM. The etiology of PCM-induced defects in macrophage function and intracellular signaling remain unknown but may be related to the neuroendocrine response to PCM. (C) 1998 Academi c Press.