POLYMYXIN-B PREVENTS INCREASED SYMPATHETIC ACTIVITY AND ALVEOLAR MACROPHAGE TUMOR-NECROSIS-FACTOR RELEASE IN PARENTERALLY FED RATS

Objective: To determine the effects of polymyxin B sulfate in rats fed by total parenteral nutrition on norepinephrine excretion, macrophage tumor necrosis factor production, and bacterial translocation. Design : Randomized animal study. Materials and Methods: Three groups of rats were studied: chow plus intravenous saline, total parenteral nutritio n, or total parenteral nutrition supplemented with polymyxin B sulfate . After 5 days, urinary excretion of norepinephrine and epinephrine wa s calculated, peritoneal and alveolar macrophages were cultured, and t heir spontaneous and lipopolysaccharide-stimulated tumor necrosis fact or production was measured. Mesenteric lymph nodes were cultured for b acteria. Results: Rats fed by total parenteral nutrition had increased urine norepinephrine excretion (33%) and alveolar macrophage tumor ne crosis factor production (80%) and trends for increased epinephrine ex cretion and bacterial translocation compared with rats fed chow. Alveo lar but not peritoneal macrophage tumor necrosis factor production was significantly related to norepinephrine excretion (r = .5, P < .01). The addition of polymyxin B to total parenteral nutrition decreased we ight gain (P < .05), urinary norepinephrine excretion (P < .01), and a lveolar macrophage tumor necrosis factor production (P < .05) compared with rats fed by total parenteral nutrition. Polymyxin B also tended to decrease the magnitude of bacterial translocation. Conclusions: Alv eolar macrophage tumor necrosis factor production appears to be influe nced by sympathetic nervous activity. Total parenteral nutrition-induc ed endotoxemia may indirectly alter macrophage function by stimulating sympathetic nervous activity.