PARENTERAL-NUTRITION ALTERS MONOCYTE TNF RECEPTOR ACTIVITY

The route of nutrient provision has been reported to influence some as pects of the host inflammatory response in both patient populations an d normal subjects. The tumor necrosis factor receptor system is a comp lex regulatory mechanism that modulates the bioavailability of tumor n ecrosis factor (TNF). We sought to determine whether maintenance on to tal parenteral nutrition (TPN) can alter host response to endotoxin ch allenge, specifically as it relates to the TNF receptor system. Sevent een healthy men were randomized to receive either TPN (n = 8) or a def ined formula enteral diet (ENT, n = 9) prior to intravenous infusion o f endotoxin (Lot EC-5, 20 U/kg). The subjects that received 1 week of antecedent TPN exhibited an increased heart rate and temperature and d ecreased mean arterial pressure post-LPS compared to those subjects ma intained on enteral nutritional support. The TPN subjects also exhibit ed comparatively higher TNF and interleukin-6 levels in response to en dotoxin. Monocyte TNF receptor levels decreased in both groups post-LP S, 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 hi gher in the enterally fed group. From these studies it appears that an tecedent TPN not only influences clinical manifestations of endotoxin but also modulates the regulation of all associated TNF receptors and shedding of soluble receptors. (C) 1995 Academic Press, Inc.