The neuropeptide bombesin improves IgA-mediated mucosal immunity with preservation of gut interleukin-4 in total parenteral nutrition-fed mice

Abstract

Background: The Th2 cytokines, interleukin-4 (IL-4) and interleukin-10 (IL-10), stimulate IgA production. Total parenteral nutrition (TPN) reduces IL-4 and IL-10 messenger RNA in gut lamina propria lymphocytes, total IL-4 and IL-10 in gut homogenates, and IgA-mediated mucosal immunity. Bombesin (BBS) can maintain mucosal immunity in TPN-fed mice, but the effects of BBS on gut IL-4 and IL-10 levels and their mRNA expression in the lamina propria are unknown.

Methods: In experiment 1, mice that were fed chow, TPN, or TPN + BBS (15 microg/kg intravenously-three times a day) for 5 days were killed, and respiratory tract IgA and intestinal IgA, IL-4, and IL-10 levels were measured. In experiment 2, IL-4 and IL-10 mRNA were measured in isolated lamina propria lymphocytes from chow-, TPN-, and TPN+BBS-fed mice by reverse transcriptase-polymerase chain reaction. Intestines were harvested 1 hour after injection of 100 7 microg of lipopolysaccharide intraperitoneally. Samples were standardized to beta-actin.

Results: TPN-fed mice had significantly lower respiratory tract IgA levels than chow- or TPN + BBS-fed mice. TPN+BBS did not increase intestinal IL-10 or IL-10 lamina propria mRNA levels but maintained intestinal IL-4 levels and lamina propria IL-4 mRNA expression equal to those of chow-fed mice.

Conclusions: BBS reverses the effects of TPN on intestinal and respiratory tract IgA levels and most effects on gut cytokines. Lamina propria cytokine mRNA levels reflect total gut cytokine concentration.