IMPAIRMENT OF PULMONARY MACROPHAGE FUNCTION WITH TOTAL PARENTERAL-NUTRITION

Objective The effects of total parenteral nutrition (TPN) administrati on on pulmonary macrophage function and host response to gram-negative pulmonary infection were evaluated. Summary Background Data Administr ation of TPN resulted in increased infectious complications in traumat ized and perioperative patients, but underlying mechanisms are unclear . Methods Twenty-six male Wistar rats underwent central vein cannulati on and were randomized to isocaloric feeding of a regular chow diet (R D) plus saline infusion or TPN without chow diet for 7 days. Pulmonary alveolar macrophage (PAM phi) superoxide production, Candida albicans phagocytosis and killing, and tumor necrosis factor(TNF) production i n response to endotoxin (LPS) were assessed. Mesenteric lymph nodes(ML N) were cultured. A second group of rats (n = 6/group) were inoculated intratracheally with a sublethal dose of 9 X 10(9) live Escherichia c oil per animal, and the lungs were cultured quantitatively 72 hours la ter to assess bacterial clearance. Finally, 11 RD-fed rats and 13 TPN- fed rats received intratracheal inoculation of 1.4 X 10(10) live E. co li and were included in follow-up. Results Administration of TPN was a ssociated with a significant increase in bacteria positive MLN compare d with those in the RD group (p < 0.01). Pulmonary alveolar macrophage superoxide production, Candida albicans phagocytosis and killing, TNF production, and pulmonary clearance bf bacteria were decreased signif icantly in TPN-fed rats compared with those fed a regular chow diet (p < 0.05). These pulmonary macrophage function changes were associated with a significantly higher mortality in TPN-fed rats compared with RD -fed rats after higher dose pulmonary E. coli inoculation. Conclusions Defective host pulmonary antimicrobial immune responses during TPN ar e associated with intestinal bacterial translocation, and may explain increased infectious complications.