Polymyxin B prevents increased sympathetic activity and alveolar macrophage tumor necrosis factor release in parenterally fed rats
K. M. Johnson, R. M. Garcia, M. Heitkemper and W. S. Helton
Department of Surgery, University of Washington, Seattle, USA.
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. SETTING: A university teaching hospital in Seattle, Wash.
MATERIALS AND METHODS: Three groups of rats were studied: chow plus
intravenous saline, total parenteral nutrition, or total parenteral
nutrition supplemented with polymyxin B sulfate. After 5 days, urinary
excretion of norepinephrine and epinephrine was calculated, peritoneal and
alveolar macrophages were cultured, and their spontaneous and
lipopolysaccharide-stimulated tumor necrosis factor production was
measured. Mesenteric lymph nodes were cultured for bacteria. RESULTS: Rats
fed by total parenteral nutrition had increased urine norepinephrine
excretion (33%) and alveolar macrophage tumor necrosis factor production
(80%) and trends for increased epinephrine excretion and bacterial
translocation compared with rats fed chow. Alveolar 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 weight gain (P < .05), urinary
norepinephrine excretion (P < .01), and alveolar 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: Alveolar macrophage tumor necrosis
factor production appears to be influenced by sympathetic nervous activity.
Total parenteral nutrition-induced endotoxemia may indirectly alter
macrophage function by stimulating sympathetic nervous activity.
