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 total parenteral nutrition-induced impairment of upper respiratory tract immunity.

DESIGN

Randomized, controlled trial.

PARTICIPANTS

Thirty-six 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 total parenteral nutrition plus bombesin (n = 12) administered 3 times daily at 15 micrograms/kg. After 5 days, mice were rechallenged with intranasal virus and killed at 40 hours to determine viral shedding from the respiratory 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 diluted 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 group. 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 group (P < .05).

CONCLUSIONS

Exogenous administration of bombesin reversed the total parenteral nutrition-associated impairment of upper respiratory tract immunity to an IgA-mediated infectious challenge. These observations support the concept of a common mucosal immune system, since neuropeptides are endogenous to the gastrointestinal and respiratory tracts. Hormonal modulation of immunity is a promising avenue of treatment for patients who require total parenteral nutrition.