Modulation of acute lung injury (ALI) by lipid emulsions – dependency of the chemerin 23 receptor (ChemR23)?

Acute lung injury (ALI) is a major cause of morbidity and mortality in intensive care units. Lipid emulsions (LE) used for parenteral nutrition might influence patient outcome due to provision of n-6 lipids as precursors of pro-inflammatory lipid mediators. In contrast, the n-3 fatty acids (FA) and their derived lipid mediators, including resolvins, were shown to reduce inflammatory responses. The chemerin receptor 23 (ChemR23) was identified to deliver the anti-inflammatory actions of chemerins as well as resolvin E1. In a model of ALI, we determined possible effects of emulsions providing n-6 or n-3 lipids and the role of the ChemR23.

We infused wild type mice (WT) and mice lacking the ChemR23 (-/-) with LE and NaCl for two days before induction of ALI by instillation of lipopolysaccharide (LPS). Bronchoalveolar lavage (BAL) was performed, leukocytes counted, cytokines and protein concentration measured by ELISA. White blood cells were counted in blood samples.

24h after induction of ALI in WT receiving NaCl, we detected an increase in leukocytes and protein while cytokines were unchanged. ChemR23-/- showed higher levels of leukocytes and protein compared to WT. After infusion of WT with LE rich in n-3 FA, the rise in leukocytes and protein was slightly reduced whilst n-6 FA-based LE caused no further increase. ChemR23-/- mice did exhibit a reduction in intraalveolar leukocytes after infusion of either LE.

The lack of ChemR23 amplifies the inflammatory response, hence illustrating its significance in controlling inflammation. The selection of LE used in critically ill patients may possibly effect the outcome of those patients as they influence inflammatory responses with the ChemR23 seeming to be necessary to mediate this reaction. Deletion of the ChemR23 does not annihilate the possible beneficial effects of n-3 fatty acids. This suggests that this receptor for resolvin E1 is not the key player.