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ObjectiveTo study the ability of bombesin (BBS) to recover gut-associated lymphoid tissue (GALT) and preserve immunity in a lethal model of Pseudomonas aeruginosa (Ps) pneumonia in mice receiving total parenteral nutrition (TPN). Summary Background DataTPN causes depression of mucosal immunity compared with enterally fed animals, 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 IgA-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. MethodsMale 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 then were killed to harvest Peyer's patch, intraepithelium, and lamina propria for cell yields. Gastrointestinal and respiratory tract IgA levels were analyzed by enzyme-linked immunosorbent assay. Next, mice underwent intranasal inoculation with liposomes alone (nonimmune) or liposome-containing Ps polysaccharide. Ps immune mice were catheterized and randomized to chow, IV TPN, or IV TPN ϩ BBS. The liposome group received chow but no IV catheter. These mice were given an LD 90 dose of intratracheal Ps, and death rates were recorded. ResultsGALT and gastrointestinal and respiratory tract IgA levels improved to those 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. TPN-fed animals lost their mucosal immunity, with a death rate of 86% compared with 21% in the TPN ϩ BBS group. ConclusionThe results demonstrate that BBS reverses TPN-induced changes in GALT and preserves mucosal immunity. Ps immunization reduces the death rate in a gram-negative pneumonia model and maintains gastrointestinal and respiratory immunity in Ps immune mice receiving IV TPN.Nosocomial pneumonia accounts for approximately 15% of hospital-acquired infections 1 and 18 pneumonias per 1,000 ventilator days in the adult intensive care unit.2 The overwhelming majority of bacterial isolates in these cases are aerobic gram-negative bacilli. Pseudomonas aeruginosa (Ps) was identified as the causative agent in 17% to 31% [3][4][5] of the cases, with a subsequent death rate of 40% to 70%. 6,7 Although many etiologic factors, such as prolonged mechanical ventilation, acute pulmonary injury, and aspiration, influence the risk of pneumonia, nutrition also appears to play an important role. In clinical studies of trauma patients, those fed intravenously have a significantly higher incidence of pneumonia and intraabdominal abscess than those fed enterally. 8 -10 Although the mechanism for this increased susceptibility to infection is unclear, our work suggests that enteral feeding improves the function of the major source of mucosal immunity-the gut-associated ly...