Abstract
Introduction: Bacterial pneumonia (PNA) is the most common cause of ARDS across all ages. In the aging population, there is a marked increased in morbidity and mortality after PNA. Age-related dysregulation of alveolar and lung macrophages has been reported to contribute to an unremitting pro-inflammatory state.
Aim: To determine if sustained aging-related lung pro-inflammatory macrophages can be reprogrammed and promote resolution of PNA in the aging host.
Methods: Adult (24-week-old) and aged (80-weeks-old) C57BL6 male WT mice were used. An infectious PNA-ARDS model was used by intratracheal instillation (IT) of 1x10^6 CFU of live Streptococcus pneumoniae in both groups. Intraperitoneal administration of IL-4 complex was used as a rescue treatment on days 2, 3 and 4 after PNA. Bronchoalveolar lavage (BAL), lung and spleen were collected at day 6 for cell count differential, protein quantification, and high dimensional flow cytometry.
Results: In contrast to young, older mice displayed impaired resolution of PNA a defect that was restored by exogenous IL-4. BAL protein, BAL cells and lung total cell counts were lower in the young and old IL-4 treated mice. Immune phenotyping of the treated groups showed increased expression of M2 markers in interstitial macrophages such IL-10, MMR2 and Dectin-1 and lower M1 markers such as CD64 and CD86.
Conclusion: Enhancing the polarization of aged macrophages towards an M2 pro-repair phenotype could represent a novel target for promoting lung injury resolution in the aging host.
Footnotes
Cite this article as Eur Respir J 2022; 60: Suppl. 66, 4258.
This article was presented at the 2022 ERS International Congress, in session “-”.
This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).
- Copyright ©the authors 2022
