Altered macrophage intracellular signaling induced by protein-calorie malnutrition.

Protein-calorie malnutrition (PCM) contributes to increased morbidity and mortality through impairment of host defense mechanisms and reduced macrophage function. The present study examined alterations in macrophage intracellular signaling associated with the impairment in host defense capabilities. Mice were randomized to either control (regular diet) or protein-free diets (PCM) and pair-fed for 1 week. Following endotoxin stimulation, peritoneal macrophages from PCM mice produce significantly less TNF-alpha and IL-6 product and had significantly less cell-associated IL-6 when compared to macrophages from control mice. Similarly, macrophages from PCM mice had a significant reduction in mRNA levels for both TNF-alpha and IL-6. Other macrophage intracellular signaling mechanisms, such as calcium flux and tyrosine kinase phosphorylation 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.