Presented at the Neonatal Society 2002 Spring Meeting.

Clark H, Reid KBM (introduced by Professor A R Wilkinson)

MRC Immunochemistry Unit and Department of Paediatrics, University of Oxford, UK

Infective episodes, oxidative lung injury and defective alveolar remodelling are all considered to increase the risk of neonatal chronic lung disease (CLD). SP-D deficient mice develop chronic lung inflammation with increased numbers of abnormal alveolar macrophages, excess alveolar phospholipid, increased reactive oxygen species and the development of pulmonary fibrosis and emphysema. To assess if this process could be modulated by exogenous SP-D treatment, SP-D knock-out mice received recombinant human SP-D (rhSP-D) for 3 to 6 weeks. After 3 weeks of rhSP-D therapy, the excessive number of alveolar macrophages in bronchoalveolar lavage (BAL) from knock-out mice was 50% lower than in untreated controls (p<0.05, n=6 mice each group). BAL phospholipid levels were significantly lower after 6 weeks of rhSP-D treatment (p< 0.05, n= 6 mice each group). Levels of granulocyte monocyte colony stimulating factor (GMCSF) in BAL and lung mRNAs for the proinflammatory chemokines monocyte chemoattractant protein 1 (MCP-1) and macrophage inflammatory protein 1a (MIP-1a) were increased in SP-D knock-out mice compared to wild-type (p<0.01), but were reduced after rhSP-D treatment (p< 0.05). The results show that rhSP-D modulates macrophage mediated inflammation in mice susceptible to emphysematous change because of SP-D deficiency, and suggest that replacement of SP-D in surfactant deficient preterm babies could help reduce the risk of CLD.