Poster Presentation Lorne Infection and Immunity 2022

Investigating IL-37 in the setting of bronchopulmonary dysplasia (BPD) (#153)

Steven Garrick 1 2 , Christine Bui 1 , Marcel F Nold 1 3 4 , Jane E Bourke 2 , Claudia Nold-Petry 1 4
  1. Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, Australia
  2. Pharmacology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia
  3. Monash Newborn, Monash Children’s Hospital, Melbourne, VIC, Australia
  4. Department of Paediatrics, Monash University, Melbourne, VIC, Australia

Introduction.  BPD is a lung disease of premature babies characterised by reduced lung function that is primarily mediated by inflammation.  The interleukin (IL)-1 family of cytokines/receptors has regulatory roles in both driving and opposing inflammation but remains largely undescribed in BPD.  The broadly acting anti-inflammatory cytokine IL-37 is of particular interest, as it reduces proinflammatory factors, such as IL-1β, that are elevated in infants with BPD. 

Aims.  To subject wild-type (Wt) and IL-37 transgenic (IL-37tg) mice to a 28-day model of murine BPD to investigate changes in alveolar structure, airway remodeling and expression of IL-1 family members.

Methods.  In an established murine “double hit” model of BPD, pregnant dams were injected with 150 µg/kg LPS i.p. at embryonic day 14.  At birth, Wt and IL-37tg pups were randomised into normoxia (air; 21% O2) or hyperoxia (hyp; 65% O2) to give 4 groups (1) air Wt (2) air IL-37tg (3) hyp Wt and (4) hyp IL-37tg.  Lungs were prepared for alveolar and airway histology and morphometry (day 28).  Changes in lung IL-1 family mRNA expression relative to air Wt were determined by real time PCR (day 5 and 28).

Results.  Hyp Wt pups developed a severe BPD-like lung disease, with fewer, larger alveoli, reduced surface area for gas exchange and increased alveolar epithelial thickness.  Hyp IL-37tg mice were not protected against these changes.  Of note, IL-37 mRNA expression levels were reduced at day 28 of the model in air IL-37tg when compared to day 5 air IL-37tg (62 fold, p<0.05).  Additionally, at day 28, a trend for lower mRNA expression of the IL-37 co-receptor SIGIRR was observed in the lungs of air IL-37tg pups, as compared to air Wt pups.

Discussion.  IL-37tg mice were not protected against the hyperoxia-induced changes in lung morphology observed at day 28 in Wt mice, potentially due to insufficient levels of IL-37 or downregulation of its receptors.  Daily administration of recombinant IL-37 to achieve steady state levels may be required to establish the protective role of IL-37 in murine BPD.