Protein kinase C‐delta inhibition is organ‐protective, enhances pathogen clearance, and improves survival in sepsis

摘要: Sepsis is a leading cause of morbidity and mortality in intensive care units. Previously, we identified Protein Kinase C-delta (PKCδ) as an important regulator the inflammatory response sepsis. An issue development anti-inflammatory therapeutics risk immunosuppression inability to effectively clear pathogens. In this study, investigated whether PKCδ inhibition prevented organ dysfunction improved survival without compromising pathogen clearance. Sprague Dawley rats underwent sham surgery or cecal ligation puncture (CLP) induce Post-surgery, PBS inhibitor (200µg/kg) was administered intra-tracheally (IT). At 24 hours post-CLP, there evidence lung kidney dysfunction. decreased leukocyte influx these organs, endothelial permeability, gas exchange, reduced blood urea nitrogen/creatinine ratios indicating protection. significantly bacterial levels peritoneal cavity, spleen but did not exhibit direct bactericidal properties. Peritoneal chemokine levels, neutrophil numbers, macrophage phenotypes were altered by inhibition. macrophages isolated from inhibitor-treated septic demonstrated increased phagocytosis. Importantly, survival. Thus, associated with phagocytic activity, enhanced clearance, injury.