RT Journal Article
SR Electronic
T1 IL-4 mediated-macrophage reprograming promotes ARDS resolution in the Aging Host
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 4258
DO 10.1183/13993003.congress-2022.4258
VO 60
IS suppl 66
A1 A F Villabona-Rueda
A1 X Chen
A1 J Walston
A1 P Abadir
A1 F D’Alessio
YR 2022
UL http://erj.ersjournals.com/content/60/suppl_66/4258.abstract
AB 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.FootnotesCite 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).