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Chronic feeding with enteral immune-enhancing diets (IEDs) provides benefits based on composition of the diet, route of feeding, and timing of feeding in relation to timing of trauma or surgery. Our prior studies of acute feeding in naïve rats demonstrated that IED promotes blood flow and proinflammatory cytokines in the ileum. We hypothesized that chronic feeding with IED would shift gut immune status to an anti-inflammatory state during chronic sepsis, resulting in an altered state of cytokine expression in the gut. Five days prior to feeding, gauze was implanted subcutaneously in the backs of male Sprague-Dawley rats, which were fed for 3 days with either control diet (CD, Boost; Mead-Johnson, Evansville, IL) or IED (Impact; Novartis) and randomly assigned to one of four groups: saline control (NS) + control diet (CD), sepsis (EC) + CD, NS + IED, or EC + IED. EC rats were inoculated with 10(9) CFU Escherichia coli and 10(9) CFU Bacteroides fragilis in 2 ml normal saline into the back sponge while NS rats received 2 mL normal saline alone. After 3 days, animals were anesthetized and gut tissue samples were harvested and frozen at -80 degrees C. Tissue protein was extracted and ELISA was performed for interleukin (IL-1beta, IL-5, IL-6, IL-10, tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma. In saline controls, IED feeding decreased IL-1beta, IL-5, IL-6, TNF-alpha, and IFN-gamma and increased IL-10 compared with CD-fed animals. In septic animals, IED feeding increased IL-5 and IL-6, while decreasing IFN-gamma and IL-10 in the distal third of the small intestine compared with CD-fed septic rats, whereas IL-1beta and TNF-alpha levels were unchanged. Chronic IED feeding produced a anti-inflammatory state via decreased IFN-gamma and increased IL-5 and IL-6, which both promote gut IgA class switching, suggesting that the gut is shifted toward humoral immunity during chronic IED feeding in septic rats.