Interaction entre ventilation mécanique et traumatisme à la moelle épinière : réponses inflammatoires pulmonaires et médullaires
Spinal cord injury is a major cause of excessive local inflammation characterized by a massive increase in inflammatory cells and oxidative reactions. It can also enhance systemic inflammatory response through the bloodstream. Cervical spinal cord lesions can result in respiratory failure due to weakness or paralysis of respiratory muscles and may lead a patient to require respiratory support. Although mechanical ventilation is the current therapy of choice applied to injured patients for respiratory insufficiency, evidence has shown that it can directly contribute to inflammatory response and lung damage. Currently, interplay between spinal cord injury and mechanical ventilation, essential to maintain the balance of respiratory exchanges, is unknown. To protect tissues, cells and organs, the body implements a wide range of inflammatory responses in various locations. We believe that the immune response can be modulated by this interplay under the influence of the main cellular source of cytokines for host defense; the macrophage. Macrophages have recently been classified into two phenotypes: 1) classical activation (M1) and 2) alternative activation (M2) and, as of today, it is unknown through which activation profile the immune response manifests itself. M1 phenotype is GM-CSF-driven, and also induced or primed by interferon-ɣ and lipopolysaccharide. In contrast, M2 phenotype is M-CSF-driven and induced also by IL-4 and IL-13 or IL-21. M1 release mainly IL-1β, IL-6, TNF-α and MIP-1α whereas M2 produce mainly IL-10 and MCP-1.The application of respiratory support may lead to an additional inflammatory risk to the injury site that may affect distal spinal cord tissues via the systemic inflammatory responses thus amplifying damage to the spine. There is currently no therapy which has shown beneficial effects towards a real functional recovery of spinal cord injury. It seems important to determine if and how mechanical ventilation may affect the post-traumatic inflammation in both lung and at injury site. This work was aimed to better characterize the relationship between inflammation induced by a spinal cord injury and ventilation thus providing a deeper understanding of the activated inflammatory mechanisms in this context. The study was conducted in an animal model and we wanted to evaluate: 1) if spinal cord injury impacts lung inflammatory responses induced by mechanical ventilation including alveolar macrophage phenotype and 2) determine whether mechanical ventilation may alter inflammatory responses of distal spine tissues. Interplay between spinal cord injury and inflammation-induced by mechanical ventilation on lung and local spine was interpreted through analyses of inflammatory cells in broncho-alveolar lavages and spinal cord tissues after 24 hours. These analyses have shown a specific cytokines profiles both in the lung and at local site of injury. It also revealed that the application of mechanical ventilation induced a pro-inflammatory environment favoring the M1 phenotype. Conversely, a thoracic spinal cord injury in non-ventilated animals, showed that an immune response had been activated favoring an anti-inflammatory environment M2 phenotype in the lung. Cervical lesion also induced a different cytokine profile and oxidative stress responses in the lung induced by ventilation have been reduced significantly. In addition, spinal cord injury induced pro-inflammatory cytokines IL-6 expression and mechanical ventilation has been decreased IL-1β and increased TNF-α in spine tissues. In retrospect, this work provide the first evidence that ventilation induced a predominant M1 phenotype and that spinal cord injury modulated specific inflammatory and oxidative stress responses in the lung. In addition, mechanical ventilation not only contributed to local inflammation in distal spinal injured tissues but also in healthy tissues.
Inflammation Cytokines Macrophages mechanical ventilation Spinal cord injury Inflammation Cytokines Macrophages Phenotype Oxidative Stress