Background: Gut derived mediators and immune cells released into the mesenteric lymph during abdominal sepsis cause severe pulmonary dysfunction including activation of macrophages (Glatzle JOGS 2007). Long chain fatty acids absorbed in the gut activate a vago-vagal reflex pathway, the so called “cholinergic anti-inflammatory pathway”, which controls the activity of macrophages in the gut wall (Wang Nat. Med. 2004). Aim: To investigate whether an enteral immunonutrition with long chain fatty acids prevents the activation of macrophages in the gut wall. Methods: Mesenteric lymph was obtained from lymph fistula rats, receiving an enteral infusion of either 5%glucose (glucose lymph) or long chain fatty acids in form of 2% olive oil (lipid lymph) before and after LPS (e-coli 5mg/kg i.p.) injection. Lymph was used for isolation of immune cells (analysed with FACS) and for measurement of TNFα. The immune cells (≈10⁶) were stimulated invitro with LPS (10ng, 100ng, 1µg, 10µg). TNFα was measured in all lymph samples and in the supernatant of the invitro experiments. Results: Sepsis induced by LPS increased TNFα release into the mesenteric lymph about 240 fold in glucose-treated rats, which was significantly reduced in lipid treated rats (TNFα pg/ml, before vs. after LPS, glucose lymph: 44±12 vs. 10680±1400*; lipid lymph: 33±15 vs. 2330±1297*; * p<0.005 glucose vs. lipid). Sepsis induced a significant 2 fold increase in the release of CD11c/ED2 positive macrophages in both glucose and lipid treated animals; there was no difference between glucose or lipid treated rats. LPS induced a significantly greater increase in release of TNFα in macrophages harvested from mesenteric lymph during enteral glucose vs. lipid infusion (TNFα pg/ml, glucose vs. lipid, 100ng LPS: 87±23 vs. 28±20*; 1µg LPS: 60±9 vs. 4±2*, p<0.01 vs. glucose). Conclusions: During sepsis, macrophages in the gut wall are activated releasing inflammatory mediators such as TNFα. However, an enteral immune modulating diet with long chain fatty acids in form of olive oil was able to suppress TNFα release from macrophages in the gut. This is possibly mediated through the cholinergic anti-inflammatory pathway, thereby preventing the release of disease-inducing cytokines into the circulation. (Supported by the German Sepsis Foundation)