Sepsis-Induced Lung Injury Mechanisms and Therapeutic Interventions

Sepsis-induced lung injury arises from a dysregulated host response to infection, whereby pathogen-associated molecular patterns trigger an overwhelming inflammatory cascade. Activation of innate immune cells leads to release of proinflammatory cytokines, complement activation and neutrophil sequestration in the pulmonary microvasculature. This disrupts the alveolar-capillary barrier, resulting in protein-rich oedema, surfactant inactivation and impaired gas exchange. Contributing factors include oxidative stress, mitochondrial dysfunction, endothelial and epithelial apoptosis, dysregulated coagulation and surfactant depletion. Standard management comprises early antimicrobial therapy, haemodynamic support and lung-protective ventilation. Emerging approaches aim to target specific molecular pathways: inhibition of NF-κB and NLRP3 inflammasome to limit cytokine storms; activation of PI3K/Akt/mTOR signalling to preserve barrier integrity; antioxidant therapies to neutralise reactive oxygen species; and application of natural or synthetic small molecules that restore mitochondrial function or attenuate endothelial injury. Precision immunomodulation, cell-based therapies and nanoparticle-mediated drug delivery are under investigation. Biomarker-guided stratification seeks to tailor interventions to individual immune phenotypes. By integrating mechanistic insights with clinical strategies, current research aspires to reduce the global burden of sepsis-induced acute respiratory distress and improve patient outcomes.

Research from Nature Portfolio

No recent Nature Portfolio content available.

Sepsis-Induced Lung Injury Mechanisms and Therapeutic Interventions publication trend

The graph below shows the total number of articles in sepsis-induced lung injury mechanisms and therapeutic interventions across all publications each year (not limited to Nature Index journals).

Technical terms

Alveolar-capillary barrier: The interface of the pulmonary endothelium and epithelium that regulates fluid and solute exchange between the blood and alveolar airspace.

Cytokine storm: An excessive and dysregulated release of proinflammatory cytokines that contributes to multi-organ dysfunction during severe infection.

NLRP3 inflammasome: A multiprotein complex in innate immune cells that activates caspase-1, promoting maturation and release of interleukin-1β and interleukin-18 in response to danger signals.

PI3K/Akt/mTOR pathway: A key cell signalling axis that governs cell survival, metabolism and barrier integrity within endothelial and epithelial tissues.

References

1. Mechanisms of Sepsis-Induced Acute Lung Injury and Advancements of Natural Small Molecules in Its Treatment. Pharmaceuticals (2024).
2. Mitochondrial Coenzyme Q Protects Sepsis‐Induced Acute Lung Injury by Activating PI3K/Akt/GSK‐3β/mTOR Pathway in Rats. BioMed Research International (2019).
3. Osthole Protects against Acute Lung Injury by Suppressing NF‐κB‐Dependent Inflammation. Mediators of Inflammation (2018).