A critical role for the IL-1 receptor in lung injury induced in neonatal rats by 60% O2.
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% O2 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% O2 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 microm) and alveolar numbers. Lung IL-1 alpha and -1 beta contents were increased after a 4-d exposure to 60% O2. 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% O2-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% O2-induced chronic neonatal lung injury.
Johnson
Ben-Hur
BH
Department of Paediatrics, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
Yi
Man
M
Masood
Azhar
A
Belcastro
Rosetta
R
Li
Jun
J
Shek
Samuel
S
Kantores
Crystal
C
Jankov
Robert P
RP
Tanswell
A Keith
AK
D042683:Angiopoietin-1 / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight; D053590:Interleukin 1 Receptor Antagonist Protein / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D055370:Lung Injury / Q000209:etiology*; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism; D009929:Organ Size; D010100:Oxygen / Q000009:adverse effects*; D010586:Phagocytes / Q000378:metabolism; D051381:Rats; D017472:Receptors, Interleukin-1 / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism
D042683:Angiopoietin-1; D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D017472:Receptors, Interleukin-1; D042461:Vascular Endothelial Growth Factor A; D014443:Tyrosine; C501163:Flt1 protein, mouse; D040281:Vascular Endothelial Growth Factor Receptor-1; D010100:Oxygen