Route and type of nutrition influence IgA-mediating intestinal cytokines

Objective To examine the levels of a Th1 IgA-inhibiting cytokine (interfero n gamma) and the Th2 IgA-stimulating cytokines (interleukin [IL]-4, IL-5, I L-6, and IL-10) within the intestine of animals manipulated with enteral or parenteral nutrition, and to correlate these cytokine alterations with int estinal IgA levels, SummaryBackground Data Enteral feeding significantly reduces the incidence of pneumonia in critically injured patients compared with intravenous total parenteral nutrition (IV TPN) or no nutritional support. Experimentally, c omplex diets prevent impairments in mucosa immunity induced by IV TPN. Thes e impairments include decreases in intestinal and respiratory tract IgA lev els, impaired IgA-mediated antiviral defenses, and increases in the mortali ty rate against established immunity to Pseudomonas pneumonia. Intragastric (IG) TPN maintains antiviral defenses but only partially preserves protect ion against Pseudomonas pneumonia. Because IgA levels depend on interaction s between Thl IgA-inhibiting and Th2 IgA-stimulating cytokines, the authors postulated differences in gut cytokine balance in enterally and parenteral ly fed mice. Methods Sixty-one mice were randomized to receive chow, IV TPN, IG TPN, or an isocaloric, complex enteral diet. After 5 days of feeding, animals were killed and supernatants from samples of intestine were harvested, homogeniz ed, and assayed for Thl and Th2 cytokines by enzyme-linked immunosorbent as say. Results The Th2 cytokines, IL-5 and IL-6,and the Th1 cytokine, interferon g amma, remained unchanged by diet. IL-4 levels decreased significantly in bo th IV and IG TPN groups Versus the chow or complex enteral diet groups, whe reas IL-10 decreased only in IV TPN mice. Decreases in Th2 cytokines correl ated with intestinal IgA levels. Conclusion Chow and complex enteral diets maintain a normal balance between IgA-stimulating and Iga-inhibiting cytokines while preserving normal antib acterial and antiviral immunity. The IgA-stimulating cytokine IL-4 drops si gnificantly in mice receiving IG and IV TPN in association with reduced IgA levels, whereas IL-10 decreases significantly only in mice receiving IV TP N. These data are consistent with severely impaired mucosal immunity with I V TPN and partial impairment with 1G TPN and provide a cytokine-mediated ex planation for reduction in diet-induced mucosal immunity.