Interleukin-7 treatment reverses parenteral nutrition-induced impairment of resistance to bacterial pneumonia with increased secretory immunoglobulin A levels.

BACKGROUND

Absence of enteral delivery of nutrients causes gut associated lymphoid tissue (GALT) atrophy and an imbalance between immunoglobulin A (IgA)-inhibiting Th1 and IgA-stimulating Th2 cytokine levels in the gut, leading to impaired mucosal immunity. We previously demonstrated exogenous IL-7 to reverse parenteral nutrition (PN)-induced GALT cell loss but not to normalize the gut cytokine imbalance or reduce secretory IgA levels, in uninjured mice. Herein, we examined effects of exogenous IL-7 during PN on survival and IgA levels after intra-tracheal bacterial challenge.

METHODS

Sixty-five male Institute of Cancer Research (ICR) mice were randomized to chow, PN or PN+IL-7 (1 μg/kg, administered i.v. twice a day), and jugular vein catheters were inserted. The chow and PN mice received normal saline i.v. infusions instead of IL-7. After 5 d of feeding (chow or PN) and treatment, 8 × 10(7)Pseudomonas aeruginosa were instilled intra-tracheally. Survival was observed in 41 mice, while 24 were killed at 6 h after challenge and small intestinal, nasal and bronchoalveolar washings were obtained for IgA measurement.

RESULTS

PN significantly reduced survival time and IgA levels in small intestine and bronchoalveolar washings compared with chow feeding. IL-7 treatment restored these parameters. Therefore, no significant differences in survival or secretory IgA levels were found between the chow and PN+IL-7 groups.

CONCLUSIONS

Exogenous IL-7 reverses PN-induced impairment of resistance to respiratory tract infections associated with increased secretory IgA levels.