Therapeutic S100A8/A9 blockade inhibits myocardial and systemic inflammation and mitigates sepsis-induced myocardial dysfunction
Authors' conclusion
Elevated S100A8/A9 is associated with the development of LV dysfunction in severe sepsis patients and in a mouse model of endotoxemia. Pharmacological blockade of S100A8/A9 with ABR-238901 has potent anti-inflammatory effects, mitigates myocardial dysfunction
Study context
- Population
- Patients with severe sepsis in the ICU of Linköping University Hospital, Sweden; mice with lipopolysaccharide (LPS)-induced endotoxemia
- Participants
- 62 severe sepsis patients
- Comparison
- S100A8/A9 blockade with ABR-238901 vs PBS in endotoxemic mice
Methodological detailspatient cohort, mouse endotoxemia model, S100A9-/- mice
- Patient cohort
- Mouse endotoxemia model
- S100A9-/- mice
Main finding
As reported in the abstract
- In sepsis patients, elevated plasma S100A8/A9 associated with left-ventricular (LV) systolic dysfunction and increased SOFA score
- LPS 5 mg/kg induced rapid plasma S100A8/A9 increase and acute LV dysfunction in wild-type mice
- ABR-238901 prevented (early start) and reversed (late start) LV dysfunction
- Dexamethasone did not improve cardiac function vs PBS
- S100A8/A9 inhibition reduced systemic inflammatory mediators, prevented myocardial inflammatory gene upregulation and restored myocardial mitochondrial function
- S100A9-/- mice protected against LPS-induced LV dysfunction, comparable with pharmacologic blockade; ABR-238901 gave no additional improvement in S100A9-/- mice
Original publication
Therapeutic S100A8/A9 blockade inhibits myocardial and systemic inflammation and mitigates sepsis-induced myocardial dysfunction. Crit Care. Published 29 September 2023. doi:10.
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