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.


METHODS
Randomized animal study.


METHODS
A university teaching hospital in Seattle, Wash.


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.
D000818:Animals; D018988:Bacterial Translocation / Q000187:drug effects*; D001835:Body Weight; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000652:urine; D010289:Parenteral Nutrition, Total / Q000009:adverse effects*; D011112:Polymyxin B / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D014409:Tumor Necrosis Factor-alpha; D011112:Polymyxin B; D009638:Norepinephrine