Therapeutic S100A8/A9 blockade inhibits myocardial and systemic inflammation and mitigates sepsis-induced myocardial dysfunction.

ABSTRACT:

Background and aims

The triggering factors of sepsis-induced myocardial dysfunction (SIMD) are poorly understood and are not addressed by current treatments. S100A8/A9 is a pro-inflammatory alarmin abundantly secreted by activated neutrophils during infection and inflammation. We investigated the efficacy of S100A8/A9 blockade as a potential new treatment in SIMD.

Methods

The relationship between plasma S100A8/A9 and cardiac dysfunction was assessed in a cohort of 62 patients with severe sepsis admitted to the intensive care unit of Linköping University Hospital, Sweden. We used S100A8/A9 blockade with the small-molecule inhibitor ABR-238901 and S100A9^-/- mice for therapeutic and mechanistic studies on endotoxemia-induced cardiac dysfunction in mice.

Results

SUBMITTER: Jakobsson G 

PROVIDER: S-EPMC10540409 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature