Sympathetic modulation of the host defense response to infectious challenge during recovery from hemorrhage

Background: Trauma/hemorrhage (TxHem) is associated with an immediate pro-inflammatory response that, if exaggerated or prolonged, is thought to contribute to the subsequent immunosuppression that characterizes the period after injury. Previously we have demonstrated that chemical sympathectomy (SNSx) accentuates this immediate pro-inflammatory response to TxHem. These findings suggest that the noradrenergic system plays a critical role in limiting the magnitude of the inflammatory response during TxHem and preserving the integrity of the host defense response to a subsequent infectious challenge during the period after TxHem. Objective: To examine the contribution of tissue norepinephrine to the host defense response to an infectious challenge during recovery from TxHem. Methods: Male Sprague-Dawley rats underwent SNSx (6-hydroxydopamine, i.p. daily for 3 days) prior to vascular catheter implantation. Conscious, unrestrained rats were subjected to traumatic injury (muscle crush) prior to a fixed-pressure hemorrhage (40 mm Hg for 60 min) and fluid resuscitation followed 24 h later by cecal ligation and puncture (CLP). Results: SNSx impaired the hemodynamic and thermoregulatory response to hemorrhage as indicated by decreased basal blood pressure, impaired blood pressure recovery during fluid resuscitation, and greater hypothermia after CLP. Furthermore, SNSx accentuated the TNF-α, IL-1, IL-6, and IL-10 response to TxHem + infection in plasma 6 h after CLP and in peritoneal lavage fluid 24 h after CLP. Conclusion: These results indicate that the integrity of the noradrenergic system is necessary for adequate hemodynamic, thermoregulatory, and inflammatory responses to infection during the period following TxHem.