Delayed Neutralization of IL-6 Reduces Organ Injury Selectively Suppresses Inflammatory Mediator and Partially Normalizes Immune Dysfunction following Trauma and Hemorrhagic Shock

摘要

An excessive and uncontrolled systemic inflammatory response is associated with organ failure, immunodepression, and increased susceptibility to nosocomial infection following trauma. Interleukin-6 (IL-6) plays a particularly prominent role in the host immune response after trauma with hemorrhage. However, as a result of its pleiotropic functions, the effect of IL-6 in trauma and hemorrhage is still controversial. It remains unclear whether suppression of IL-6 after hemorrhagic shock and trauma will attenuate organ injury and immunosuppression. In this study, C57BL/6 mice were treated with anti-mouse-IL-6 monoclonal antibody (anti-IL-6 mAb) immediately prior to resuscitation in an experimental model combining hemorrhagic shock and lower extremity injury (HS+T). Interleukin-6 levels and signaling were transiently suppressed following administrations of anti-IL-6mAb following HS+T. This resulted in reduced lung and liver injury, as well as suppression in the levels of key inflammatory mediators including IL-10, KC, MCP-1, and MIP-1α at both 6 and 24h. Furthermore, the shift to Th2 cytokine production and suppressed lymphocyte response were partly prevented. These results demonstrate that IL-6 is not only a biomarker but also an important driver of injury-induced inflammation and immune suppression in mice. Rapid measurement of IL-6 levels in the early phase of post-injury care could be used to guide IL-6 based interventions.