EFFECT OF BOMBESIN ON IMPAIRMENT OF UPPER RESPIRATORY-TRACT IMMUNITY INDUCED BY TOTAL PARENTERAL-NUTRITION

Objective: To determine the effect of the neuropeptide bombesin on tot al parenteral nutrition-induced impairment of upper respiratory tract immunity. Design: Randomized, controlled trial. Participants: Thirty-s ix adult male Institute for Cancer Research mice weighing 25 to 35 g. Interventions: Mice were inoculated intranasally with H1N1 virus. At 3 weeks, mice were randomized to receive chow plus intravenous saline ( n=12), intravenous total parenteral nutrition (n=12), or intravenous t otal parenteral nutrition plus bombesin (n=12) administered 3 times da ily at 15 mu g/kg. After 5 days, mice were rechallenged with intranasa l virus and killed at 40 hours to determine viral shedding from the re spiratory tract; normal convalescent mice do not shed virus because of intact IgA-mediated mechanisms. Main Outcome Measures: Viral shedding was determined by collection of nasal secretions. Samples were dilute d and incubated with a suspension of Madin-Darby canine kidney cells. Viral growth was determined by hemagglutination. Results: Body weight was similar between the total parenteral nutrition and bombesin groups ; however, both were significantly lower than that in the chow group ( P<.05). After 6 days of feeding, no mice in the chow group shed virus, compared with 6 (50%) of the mice in the total parenteral nutrition g roup. Of the mice in the bombesin group, only 1 was positive for viral shedding. The total parenteral nutrition group showed increased viral shedding compared with both the chow group (P<.01) and the bombesin g roup (P<.05). Conclusions: Exogenous administration of bombesin revers ed the total parenteral nutrition-associated impairment of upper respi ratory tract immunity to an IgA-mediated infectious challenge. These o bservations support the concept of a common mucosal immune system, sin ce neuropeptides are endogenous to the gastrointestinal and respirator y tracts. Hormonal modulation of immunity is a promising avenue of tre atment for patients who require total parenteral nutrition.