# From “metabolic storm” to “immune paralysis”: the dynamic evolution of macrophages and metabolism reprogramming in ARDS

## TL;DR

This review explores how macrophage metabolism changes during sepsis-induced ARDS and how these changes could be targeted for treatment.

## Contribution

The paper provides a comprehensive overview of macrophage metabolic reprogramming and its therapeutic implications in sepsis-associated ARDS.

## Key findings

- Macrophage metabolic reprogramming evolves from a 'metabolic storm' to 'immune paralysis' in ARDS.
- Glycolysis and oxidative phosphorylation influence macrophage polarization and lung tissue damage.
- BMMSCs and MDSCs offer potential therapeutic strategies by altering macrophage metabolism.

## Abstract

Sepsis is characterized by high mortality and a complicated pathological mechanism. Macrophages play a crucial role in the initiation and progression of sepsis-associated acute respiratory distress syndrome (ARDS). Macrophage functional states and polarization phenotype have been significantly influenced by metabolic programming. This review delineates the metabolic reprogramming of macrophages from the initial ‘metabolic storm’ to subsequent ‘immune paralysis’ in sepsis-associated ARDS. It focuses on the interplay between macrophage polarization (classical activated macrophages (M1) and alternative activated macrophages (M2) phenotypes) and key metabolic pathways, including glycolysis and oxidative phosphorylation (OXPHOS). Furthermore, it explains the molecular mechanism underlying the metabolic pattern’s influence on macrophage and lung tissue damage. The final section of this review focuses on the therapeutic implications of bone marrow mesenchymal stem cells (BMMSCs) and myeloid-derived suppressor cells (MDSCs), which alter macrophage metabolic reprogramming. Based on the latest progress, this article aims to provide a comprehensive theoretical framework and cli Based on recent advances, nical guidance for immunometabolic therapy in sepsis-associated ARDS.