Morphine exacerbates experimental sepsis by modulating IL17/IL22 response (IRC8P.488)

Abstract

Abstract Sepsis ranks as the top 10 cause of mortality in the intensive care units (ICU) in USA and the standard management of pain in these patients are opioids. However, very few studies have investigated the influence of opioids on development and progression of sepsis. In the present study, we determined the effects of morphine on sepsis progression using the murine cecal ligation and puncture model, which resembles many aspects of the human pathology. Our studies demonstrate that morphine treatment increases bacterial dissemination at the early stage of sepsis (24 hours) and significantly attenuates pathogen clearance at late stage of sepsis (72 hours). In addition, IL17a and IL22 responses to pathogen stimulation are impaired following morphine treatment, resulting in delayed neutrophil recruitment to peritoneal cavity, thereby compromising pathogen clearance. This is the first study to demonstrate that IL17a and IL22 responses play important roles in host defense against polymicrobial sepsis, and that this crucial response is impaired following opioid treatment. These studies imply that IL17a and IL22 may be potential therapeutic targets to treat or prevent sepsis, especially in opioid use and abuse population.