CX-01 Improves Survival and Attenuates Organ Failure in a Rat Polytrauma Model 2300256

Abstract

Abstract Introduction Severe polytrauma can induce devastating complications, including acute kidney injury, acute respiratory distress syndrome, and other organ failure. If left treated, these severe complications can lead to high mortality. The pathological mechanisms remain inconclusive, but innate immune dysfunction may contribute to trauma-induced organ failure. Methods Male Sprague Dawley rats were anesthetized and given proper analgesics, underwent polytrauma (soft tissue injury, fibula facture and pressure-controlled hemorrhage), received blood resuscitation to maintain a MAP of 90 mmHg, and then monitored for 72 hours, mortality, or reaching the humane endpoint. The animals were randomly assigned to either injury control (polytrauma, n = 9), or therapeutic treatment (polytrauma+CX-01, n = 7) groups. The vital signs, hemodynamics, blood chemistry, inflammation, and tissue damage were recorded and analyzed at baseline (BL), 2h, 2.5h, 24h, 48h, and 72h post-injury. Results In the injury group, 3 out of 9 animals survived to the end of the study (mortality=67%), while 6 out of 7 animals in the CX-01 treatment group survived (mortality=14%, p < 0.05). CX-01 treatment significantly reduced creatinine and BUN levels and mitigated the decline in GFR caused by polytrauma. Furthermore, CX-01 treatment reduced HMGB1 levels, inflammatory cytokines (MCP-1, RANTES, IL-10 etc.). Conclusion CX-01, as an immunotherapeutic, mitigates trauma-induced immune and organ dysfunctions, and may save lives for combat casualties. Funding Source US Army Medical Research & Development Command (Grants numbers: CO240046, CO250068 and DM230026). Topic Categories Translational and Interventional Immunology (TI)