Bombesin Recovers Gut-Associated Lymphoid Tissue and Preserves Immunity to Bacterial Pneumonia in Mice Receiving Total Parenteral Nutrition

Abstract

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...

Effects of Adding Butyric Acid to PN on Gut‐Associated Lymphoid Tissue and Mucosal Immunoglobulin A Levels

“…Lack of a direct nutrition supply from the intestinal lumen to the mucosa, absence of a GLN supply, changes in intestinal commensal bacteria, decreased neuropeptide release, and reduced IL-7 production by intestinal epithelial cells have all been suggested as important factors influencing GALT. [11][12][13][14][15][16]41 Therefore, it is not surprising that butyric acid supplementation does not completely reverse the GALT changes developing in the absence of enteral feeding. However, it is surprising that just a small alteration in the SCFA composition of PN solution significantly improved PP-cell numbers and mucosal IgA levels.…”

“…Although glutamine (GLN) supplementation of PN, neuropeptides, and interleukin 7 (IL-7) intravenous (IV) injection have been regarded as possible surrogates for EN in animal experimental models, [11][12][13][14][15][16] these therapies are far from clinical application, with the exception of GLN supplementation of PN.…”

Hyalinosis and Ym1/Ym2 Gene Expression in the Stomach and Respiratory Tract of 129S4/SvJae and Wild-Type and CYP1A2-Null B6,129 Mice

“…44,45 Both bombesin and gastrin-releasing peptide have been shown to play roles in lung morphogenesis 46,47 and in maintenance of mucosal immunity in both the gastrointestinal and respiratory tracts. 48,49 Two other possibilities are growth hormone (somatotropin) and insulin, possibly mediated by gastrin-releasing peptide. All operate within liver feedback systems and can be tissue-specific; in fact, glucose levels have been shown to regulate the effect of both bombesin and gastrin-releasing peptide.…”

Influence of Adding Pyrroloquinoline Quinone to Parenteral Nutrition on Gut‐Associated Lymphoid Tissue

“…As previous reports have demonstrated, lack of glutamine in PN solutions, less secretion of neuropeptides and IL-7 during PN, and other factors contribute to impairment of gut immunity. [42][43][44][45][46][47] The present study may add another important piece of knowledge-that PQQ is an important factor for the maintenance of gut immunity. We believe that the present results provide an important clue for developing a new PN formula preserving gut and systemic mucosal immunity.…”