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ARTICLE |

Polymyxin B Prevents Increased Sympathetic Activity and Alveolar Macrophage Tumor Necrosis Factor Release in Parenterally Fed Rats

Kevin M. Johnson, MD; Richard M. Garcia; Margaret Heitkemper, PhD; W. Scott Helton, MD
Arch Surg. 1995;130(12):1294-1300. doi:10.1001/archsurg.1995.01430120048007.
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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.(Arch Surg. 1995;130:1294-1300)

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