Parenteral nutrition alters monocyte TNF receptor activity

The route of nutrient provision has been reported to influence some aspects of the host inflammatory response in both patient populations and normal subjects. The tumor necrosis factor receptor system is a complex regulatory mechanism that modulates the bioavailability of tumor necrosis factor (TNF). We sought to determine whether maintenance on total parenteral nutrition (TPN) can alter host response to endotoxin challenge, specifically as it relates to the TNF receptor system. Seventeen healthy men were randomized to receive either TPN (n = 8) or a defined formula enteral diet (ENT, n = 9) prior to intravenous infusion of endotoxin (Lot EC-5, 20 U/kg). The subjects that received 1 week of antecedent TPN exhibited an increased heart rate and temperature and decreased mean arterial pressure post-LPS compared to those subjects maintained on enteral nutritional support. The TPN subjects also exhibited comparatively higher TNF and interleukin-6 levels in response to endotoxin. Monocyte TNF receptor levels decreased in both groups post-LPS, but TPN subjects exhibited consistently greater expression of this functional membrane-associated TNF receptor. After LPS, soluble tumor necrosis factor receptor II (sTNFr II, p75) peaked three times higher in TPN subjects than in ENT subjects. Conversely, sTNFr I (p55) was higher in the enterally fed group. From these studies it appears that antecedent TPN not only influences clinical manifestations of endotoxin but also modulates the regulation of all associated TNF receptors and shedding of soluble receptors.