The gastrointestinal tract, besides being the organ responsible for nutrient absorption, is also a metabolic and immunological system, functioning as an effective barrier against endotoxin and bacteria in the intestinal lumen.

The results confirm that activation of the coagulation and fibrinolytic systems and release of soluble inflammatory mediators are consistently observed in patients with severe sepsis syndrome. Interleukin-1 activity contributes to activation of these processes as documented by the reduction in surrogate activation markers during recombinant human interleukin-1 receptor antagonist treatment.

The findings indicate that enteral Gln supplementation caused significantly increased arterial plasma levels of Arg as a result of increased renal Arg production from circulating citrulline. Considering the multiple important biologic properties of Arg, the reported beneficial effects of Gln in catabolic states might be explained in part by increased renal Arg production.

The hemodynamic consequences of glutamine (Gln)-enriched nutrition have not been investigated. This study investigates the effects of a Gln-enriched enteral diet on organ blood flows and systemic hemodynamics. Male Fischer 344 rats (n = 24) were randomized to a group that received a 12.5% (wt/wt) Gln-enriched enteral diet or an isonitrogenous isocaloric control diet for 14 days. Blood flow measurements were performed at day 16 using 46Sc-labeled microspheres. In the Gln-enriched group, higher organ blood flows were measured in the stomach (51%), the pancreas (35%), small intestine (32%), and colon (55%), compared with controls. No differences were found in systemic hemodynamic parameters between the control and Gln-supplemented groups. A possible role for nitric oxide in this splanchnic vasodilation was investigated. Daily urinary nitrate excretion was measured during the study but showed no significant differences between the control and Gln-fed animals. No differences were found in plasma levels of the vasodilating hormone glucagon between the groups. These results show that a Gln-enriched enteral diet increased splanchnic blood flow, which was not mediated by pancreatic glucagon or increased nitric oxide production as determined by urinary nitrate excretion.

Triglyceride-rich lipoproteins can inhibit endotoxin activity in vitro and in rodents. We sought to determine whether Intralipid, a triglyceride-rich fat emulsion which in contact with plasma functions similarly to endogenous lipoproteins, can alter the human response to endotoxin. Intralipid inhibited endotoxin-induced cytokine production in human whole blood in vitro in a dose-dependent manner, with maximal inhibition (up to 70%) being achieved at a concentration of 10 g/liter. In healthy men, a bolus intravenous injection of endotoxin (lot EC-5; 20 U/kg of body weight) was given midway through a 4-h infusion (125 ml/h) of either 5% glucose (n ‫؍‬ 5) or 20% Intralipid (n ‫؍‬ 5). The infusion of Intralipid led to an increase in triglyceride levels in serum from 95 ؎ 16 to 818 ؎ 135 mg/dl prior to endotoxin administration, i.e., levels that importantly reduced cytokine production in endotoxin-stimulated whole blood. However, in vivo hypertriglyceridemia did not influence inflammatory responses to endotoxin (fever, release of tumor necrosis factor and soluble tumor necrosis factor receptors, and leukocytosis) or even potentiated endotoxin responses (release of interleukins 6 and 8 and neutrophil degranulation). Hypertriglyceridemia does not inhibit the in vivo responses to endotoxin in humans.