ObjectiveTo develop a model of established respiratory immunity against Pseudomonas aeruginosa pneumonia and to investigate the effects of route and type of nutrition on this immunity. Summary Background DataDiet influences the ability of gut-associated lymphoid tissue (GALT) to maintain mucosal immunity. Complex enteral diets and chow maintain normal GALT populations against established IgA-mediated antiviral respiratory immunity. Both intravenous and intragastric total parenteral nutrition (TPN) produce GALT atrophy, but only intragastric TPN preserves established antiviral immunity. The authors hypothesized that both GALT-depleting diets (intragastric and intravenous TPN) would impair immunity against bacterial pneumonia. Methods P. aeruginosa was administered intratracheally to determine the mortality rate at increasing doses, and liposomes containing P. aeruginosa antigens were used to generate effective respiratory immunization. In the final experiment, mice received liposomes containing P. aeruginosa antigens to establish immunity and then were randomized to chow, complex enteral diets, intragastric TPN, or intravenous TPN. After 5 days of diet, mice received live intratracheal P. aeruginosa, and the death rate was recorded at 24 and 48 hours. ResultsThe LD50 and LD10, were 9 x 107 and 12 x 107, respectively. Immunization reduced the mortality rate from 66% to 12%. This immunization was maintained in mice fed chow or a complex enteral diet and was lost in animals receiving intravenous TPN. Intragastric TPN partially preserved this respiratory immunity. ConclusionsProtection against bacterial pneumonia can be induced by prior antigenic immunization. This protection is lost with intravenous TPN, partially preserved with a chemically defined enteral diet, and completely preserved with chow or complex enteral diets. Both route and type of nutrition influence antibacterial respiratory tract immunity.Nosocomial pneumonia occurs in 10% to 25% of mechanically ventilated patients, accounting for 15% of hospital-acquired infections.' Mortality rates attributable to these pneumonias range from 7% to 30% but can reach 40% to 50% when Pseudomonas or Acinetobacter is the causative organism.2'3 Route and type of nutrition affect the risk of pneumonia in seriously injured patients. Severely injured trauma patients receiving enteral nutrition have significantly fewer pneumonias compared with patients fed parenterally, implying an impairment in mucosal defenses in patients fed Supported by NIH grant 1 ROI GM053439.
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...
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