A Critical Role for the IL-1 Receptor in Lung Injury Induced in Neonatal Rats by 60% O-2

作者：Johnson Ben Hur; Yi Man; Masood Azhar; Belcastro Rosetta; Li Jun; Shek Samuel; Kantores Crystal; Jankov Robert P; Tanswell A Keith^*

来源：Pediatric Research, 2009, 66(3): 260-265.

DOI：10.1203/pdr.0b013e3181b1bcd2

IL-1 beta, a proinflammatory cytokine, may contribute to the development of the chronic neonatal lung injury, bronchopulmonary dysplasia. Chronic neonatal lung injury was induced in rats, by exposure to 60% O-2 for 14 d from birth, to determine whether pulmonary IL-1 expression was up-regulated and, if so, whether a daily s.c. IL-1 receptor antagonist injections would be protective. Exposure to 60% O-2 for 14 d caused pulmonary neutrophil and macrophage influx, increased tissue fraction and tyrosine nitration, reduced VEGF-A and angiopoietin-1 expression, and reduced small vessel (20-65 mu m) and alveolar numbers. Lung IL-1 alpha and -1 beta contents were increased after a 4-d exposure to 60% O-2. IL-1 receptor antagonist treatment attenuated the 60% O2-dependent neutrophil influx, the increased tissue fraction, and the reduced alveolar number. Treatment did not restore VEGF-A or angiopoietin-1 expression and only partially attenuated the reduced vessel number in 60% O-2-exposed pups. It also caused a paradoxical increase in macrophage influx and a reduction in small vessels in air-exposed pups. We conclude that antagonism of IL-1-mediated effects can, in major part, protect against lung injury in a rat model of 60% O-2 induced chronic neonatal lung injury. (Pediatr Res 66: 260-265, 2009)

• 出版日期2009-9