Interleukin-33 (IL-33) Increases Hyperoxia-Induced Bronchopulmonary Dysplasia in Newborn Mice by Regulation of Inflammatory Mediators

Background: Interleukin-33 (IL-33) has been reported to affect chronic inflammation of the lungs, but its impact on hyperoxia-injured lungs in newborns remains obscure. This study aimed to investigate the role of IL-33 in the lungs of neonatal mice with hyperoxia-induced bronchopulmonary dysplasia (BPD). Material/Methods: Twenty-four C57BL/6 baby mice were randomly separated into three groups: the on-air group (N=16); the O-2 group (N=8); and the O-2 + anti-IL-33 group (N=8). Forced mechanical ventilation with oxygen-rich air (MV-O-2) was used in 16 mouse pups. The mouse pups were incubated in containers with either air or 85% O-2 for 1, 3, 7, 14, 21, and 28 days after birth. At the end of the treatment period, the mouse lungs were studied by histology, Western blot, and quantitative real-time polymerase chain reaction (qRT-PCR) to examine the expression of the pro-inflammatory mediators, including interleukin (IL)-1 beta, chemokine (CC motif) ligand 1 (CXCL-1), and monocyte chemoattractant protein-1 (MCP-1). Results: Following forced MV-O-2, increased levels of IL-33 in whole mouse lungs were associated with impaired alveolar growth and with changes consistent with BPD, including reduced numbers of enlarged alveoli, increased apoptosis, and increased expression of IL-1 beta, CXCL-1, and MCP-1. IL-33 inhibition improved alveolar development in hyperoxia-impaired lungs and suppressed IL-1 beta and MCP-1 expression and was associated with increased transforming growth factor-beta (TGF-beta) signaling, reduced pulmonary NF-kappa B activity and decreased expression of the TGF-beta inhibitor SMAD-7 in forced MV-O-2 exposed mouse pups. Conclusions: IL-33 increased hyperoxia-induced BPD in newborn mice by regulation of the expression of inflammatory mediators.