Route and type of nutrition influence IgA-mediating intestinal cytokines

Abstract

Objective: To examine the levels of a Th1 IgA-inhibiting cytokine (interferon gamma) and the Th2 IgA-stimulating cytokines (interleukin [IL]-4, IL-5, IL-6, and IL-10) within the intestine of animals manipulated with enteral or parenteral nutrition, and to correlate these cytokine alterations with intestinal IgA levels.

Summary background 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, complex diets prevent impairments in mucosal immunity induced by IV TPN. These impairments include decreases in intestinal and respiratory tract IgA levels, impaired IgA-mediated antiviral defenses, and increases in the mortality rate against established immunity to Pseudomonas pneumonia. Intragastric (IG) TPN maintains antiviral defenses but only partially preserves protection against Pseudomonas pneumonia. Because IgA levels depend on interactions between Th1 IgA-inhibiting and Th2 IgA-stimulating cytokines, the authors postulated differences in gut cytokine balance in enterally and parenterally 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, homogenized, and assayed for Th1 and Th2 cytokines by enzyme-linked immunosorbent assay.

Results: The Th2 cytokines, IL-5 and IL-6, and the Th1 cytokine, interferon gamma, remained unchanged by diet. IL-4 levels decreased significantly in both IV and IG TPN groups versus the chow or complex enteral diet groups, whereas IL-10 decreased only in IV TPN mice. Decreases in Th2 cytokines correlated with intestinal IgA levels.

Conclusion: Chow and complex enteral diets maintain a normal balance between IgA-stimulating and IgA-inhibiting cytokines while preserving normal antibacterial and antiviral immunity. The IgA-stimulating cytokine IL-4 drops significantly in mice receiving IG and IV TPN in association with reduced IgA levels, whereas IL-10 decreases significantly only in mice receiving IV TPN. These data are consistent with severely impaired mucosal immunity with IV TPN and partial impairment with IG TPN and provide a cytokine-mediated explanation for reduction in diet-induced mucosal immunity.

Figure 1. Intestinal IgA levels in different diet groups. IgA levels were significantly lower in intravenous TPN and intragastric TPN animals than in animals fed chow. Data are expressed as mean±SEM. * p < 0.05 vs. chow.

Figure 2. There was a significant correlation between IL-4 concentrations, and intestinal IgA levels correlated well. These correlations improved when the outlier (filled circle) was removed from the analysis.

Figure 3. There was a significant correlation between IL-10 concentrations in intestinal samples and luminal IgA levels. The correlations remained relatively stable when the data from the single outlier (filled circle) was removed.