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Hemoadsorption corrects hyperresistinemia and restores anti-bacterial neutrophil function
Anthony Bonavia1, Lauren Miller1, John A Kellum2,3
1Department of Anesthesiology and Perioperative Medicine, Penn State Health, Hershey, PA, USA.
Septic hyperresistinemia impairs neutrophil function, reducing bacterial clearance and reactive oxygen species (ROS) generation. Hemoadsorption therapy effectively corrects this dysfunction, offering a potential treatment for sepsis-induced immunosuppression.
Area of Science:
- Immunology
- Critical Care Medicine
- Nephrology
Background:
- Sepsis involves immune activation and suppression, with resistin, an inflammatory cytokine, playing a key role.
- Septic hyperresistinemia (elevated plasma resistin) worsens sepsis severity and outcomes, particularly with acute kidney injury (AKI).
- Elevated resistin impairs neutrophil function, including migration, hindering the initial defense against bacterial infections.
Purpose of the Study:
- To investigate the impact of hyperresistinemia on neutrophil-mediated bacterial clearance and reactive oxygen species (ROS) generation.
- To evaluate the efficacy of hemoadsorption in correcting hyperresistinemia and associated neutrophil dysfunction.
Main Methods:
- Analyzed serum resistin levels and neutrophil migration in 13 septic shock patients and 6 controls.
- In vitro experiments measured bacterial clearance and ROS generation in neutrophils exposed to hyperresistinemia.
- Assessed hemoadsorption using Amberchrome™ (AC) and CytoSorb® (CC) for resistin reduction and restoration of neutrophil function.
Main Results:
- Septic shock patients exhibited higher resistin levels, correlating with reduced neutrophil migration.
- Hyperresistinemia significantly impaired intracellular bacterial clearance and dose-dependently reduced ROS production.
- Hemoadsorption with AC and CC successfully reduced resistin levels and restored neutrophil migration, ROS generation, and bacterial clearance.
Conclusions:
- Septic hyperresistinemia inhibits neutrophil migration, bacterial clearance, and ROS generation.
- This neutrophil dysfunction is reversible with hemoadsorption therapy.
- Hemoadsorption offers a promising therapeutic strategy to improve neutrophil function and mitigate immunosuppression in sepsis.
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