Bombesin recovers gut-associated lymphoid tissue and preserves immunity tobacterial pneumonia in mice receiving total parenteral nutrition

Objective To study the ability of bombesin (BBS) to recover gut-associated lymphoid t issue (GALT) and preserve immunity in a lethal model of Pseudomonas aerugin osa (Ps) pneumonia in mice receiving total parenteral nutrition (TPN). Summary Background Data TPN causes depression of mucosal immunity compared with enterally fed anima ls, which may explain the increased incidence of pneumonia in parenterally fed trauma patients. BBS prevents this TPN-induced GALT atrophy, depressed gastrointestinal and respiratory tract IgA levels, and impaired antiviral I ga-mediated mucosal immunity. The authors examined whether some supplement could be added to TPN to avoid this GALT atrophy and lower the incidence of infectious complications in the parenterally fed animal. Methods Male mice were randomized to chow or intravenous (IV) TPN. After 5 days of IV TPN, mice received 0, 1, 2, or 3 days of BBS IV three times a day and th en were killed to harvest Peyer's patch, intraepithelium, and lamina propri a for cell yields, Gastrointestinal and respiratory tract IgA levels were a nalyzed by enzyme-linked immunosorbent assay. Next, mice underwent intranas al inoculation with liposomes alone (nonimmune) or liposome-containing Ps p olysaccharide. Ps immune mice were catheterized and randomized to chow, IV TPN, or IV TPN + BBS. The liposome group received chow but no IV catheter. These mice were given an LD90 dose of intratracheal Ps, and death rates wer e recorded. Results GALT and gastrointestinal and respiratory tract IgA levels improved to thos e in chow-fed mice after 3 days of BBS, immunization reduced the death rate from 92% in chow-fed liposome-only animals to 20% in immunized animals. TP N-fed animals lost their mucosal immunity, with a death rate of 86% compare d with 21% in the TPN + BBS group. Conclusion The results demonstrate that BBS reverses TPN-induced changes in GALT and p reserves mucosal immunity. Ps immunization reduces the death rate in a gram -negative pneumonia model and maintains gastrointestinal and respiratory im munity in Ps immune mice receiving IV TPN.