Hyperoxic lung injury has been implicated in the pathogenesis of bronchopulmonary dysplasia. While the mechanisms for this injury remain unclear, reactive oxygen species and inflammatory cytokines are thought to be important mediators in the inflammation leading to this injury. In preliminary studies we have found that neonatal rats, like human neonates, have a profound developmental delay in the production of IL-10 in the blood and lung. The role of IL-10 in the protection of oxidative injury was therefore investigated. Recombinant rat IL-10 (rrIL-10) was prepared using a baculovirus expression vector in SF9 insect cells (concentration 1.0 μg/ml). Sprague Dawley neonatal rats < 24 h old were placed in > 98% O2 or air. After 4 days of O2 or air exposure, neonates in both groups were treated daily with rrIL-10 (250 U/kg) intraperitoneally (i.p.), rrIL-10 (250 U/kg) intranasally (i.n.) or saline intranasally (i.n.). Survival for 14 days was compared: Survival (O2) 7 days 10 days 14 days Saline i.n. 1/3 (33%) 1/3 (33%) 0 % rrIL-10 i.n. 1/4 (25%) 1/4 (25%) 0% rrIL-10 i.p. 2/3 (66%) 2/3 (66%) 2/3 (66%) After 14 days of > 98% O2 there was 66% survival of rrIL-10 i.p. rats compared to 0% survival in the saline or rrIL-10 i.n. O2 groups. There was 100% survival in all air groups. We further investigated rrIL-10 i.p. (500 U/kg) vs saline controls i.p. starting with daily injections after 4 days of > 98% O2 or air. After 10 days of O2, survival of rr IL-10 i.p. animals was 6/6 (100%), significantly higher compared to 1/6 (17%) survival of saline i.p. controls in O2. We conclude that rrIL-10 given intraperitoneally may significantly enhance survival of neonatal rats during hyperoxia.
|Original language||English (US)|
|Journal||Journal of Investigative Medicine|
|State||Published - 1999|
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)