Immunometabolic reprogramming of macrophages and neutrophils in acute pancreatitis: from metabolic stress to amplification and endogenous braking
- 1Department of Laboratory Medicine, The Third Affiliated Hospital of Zunyi Medical University (The First People’s Hospital of Zunyi)
- 2Scientific Research Center, The Third Affiliated Hospital of Zunyi Medical University (The First People’s Hospital of Zunyi)
Abstract
Acute pancreatitis (AP) progression involves both the initiating acinar injury and immune responses that sustain or contain subsequent damage. This review integrates evidence on metabolic regulation in macrophages and neutrophils to examine its links to inflammatory effectors, clearance, and tissue protection. Glycolytic regulation can support inflammatory activation, while non-AP neutrophil studies show how substrate allocation supports oxidant production and neutrophil extracellular trap (NET) release. Metabolite signaling also participates in macrophage efferocytosis, repair-associated responses, and tissue antioxidant defense. Contrasting lactate effects in acinar injury and macrophage repair indicate that metabolic changes must be interpreted through their effects on particular cells and functions. We propose an integrated amplification-braking framework that connects metabolically supported inflammatory effectors to continued generation of injury-derived stimuli, and clearance, antioxidant, and repair functions to damage containment. These functions can coexist without receiving equivalent metabolic support, and protective braking is distinct from generalized immunosuppression. Evidence differs across cells and experimental systems; metabolic regulation of inflammatory activation does not by itself establish metabolic control of NET-mediated injury in AP. The framework provides a basis for evaluating whether metabolic interventions can limit damaging activity while preserving protective functions, but it is not a validated clinical model. Pairing metabolic changes with specific cellular functions and subsequent injury is central to testing these relationships.
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BibTeX
@article{ai2026immunometabolic,
title = {{Immunometabolic reprogramming of macrophages and neutrophils in acute pancreatitis: from metabolic stress to amplification and endogenous braking}},
author = {Yuanhang Ai and Longze Zhang and Aiping Wei and Jiayan Dong and Tianjing Pang and Yuanyu Zhang and Kaifeng Wu and Shifei Yao},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1976931},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1976931/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Immunometabolic reprogramming of macrophages and neutrophils in acute pancreatitis: from metabolic stress to amplification and endogenous braking
AU - Yuanhang Ai
AU - Longze Zhang
AU - Aiping Wei
AU - Jiayan Dong
AU - Tianjing Pang
AU - Yuanyu Zhang
AU - Kaifeng Wu
AU - Shifei Yao
PY - 2026
DA - 2026/10/13
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1976931
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1976931/full
AB - Acute pancreatitis (AP) progression involves both the initiating acinar injury and immune responses that sustain or contain subsequent damage. This review integrates evidence on metabolic regulation in macrophages and neutrophils to examine its links to inflammatory effectors, clearance, and tissue protection. Glycolytic regulation can support inflammatory activation, while non-AP neutrophil studies show how substrate allocation supports oxidant production and neutrophil extracellular trap (NET) release. Metabolite signaling also participates in macrophage efferocytosis, repair-associated responses, and tissue antioxidant defense. Contrasting lactate effects in acinar injury and macrophage repair indicate that metabolic changes must be interpreted through their effects on particular cells and functions. We propose an integrated amplification-braking framework that connects metabolically supported inflammatory effectors to continued generation of injury-derived stimuli, and clearance, antioxidant, and repair functions to damage containment. These functions can coexist without receiving equivalent metabolic support, and protective braking is distinct from generalized immunosuppression. Evidence differs across cells and experimental systems; metabolic regulation of inflammatory activation does not by itself establish metabolic control of NET-mediated injury in AP. The framework provides a basis for evaluating whether metabolic interventions can limit damaging activity while preserving protective functions, but it is not a validated clinical model. Pairing metabolic changes with specific cellular functions and subsequent injury is central to testing these relationships.
SN - 1664-3224
ER -