Granzyme A inhibition reduces inflammation and increases survival during abdominal sepsis

Aims: Peritonitis is one of the most common causes sepsis, a serious syndrome characterized by dysregulated systemic inflammatory response. Recent evidence suggests that Granzyme A (GzmA), serine protease mainly expressed NK and T cells, could act as proinflammatory mediator play an important role in pathogenesis sepsis. This work aims to analyze therapeutic potential GzmA peritoneal Methods: The level extracellular well activity were analyzed serum from healthy volunteers patients with confirmed peritonitis correlated Sequential Organ Failure Assessment (SOFA) score. was induced C57Bl/6 (WT) GzmA-/- mice cecal ligation puncture (CLP). Mice treated intraperitoneally antibiotics alone or combination serpinb6b, specific inhibitor, for 5 days. Mouse survival monitored during 14 days, levels some cytokines measured bacterial load diversity blood spleen at different times. Results: Clinically, elevated observed abdominal sepsis suggesting plays this pathology. In CLP model deficient mice, WT showed increased survival, which reduction markers both lavage fluid. deficiency did not influence affect replication macrophages vitro, indicating has no control. Analysis lymphoid cells following it cells. Mechanistically, we found active acts inducing TLR4-dependent expression IL-6 TNF?. Conclusions: Our findings implicate key regulator response provide solid evidences about its treatment severe