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

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.