Post-Traumatic Immunodepression : From Pathophyiology to Treatment

Abstract

Severe multiple trauma is accompanied by a systemic inflammatory response syndrome (SIRS) caused by a massive release of intracellular components called dangerassociated molecular patterns (DAMP). These DAMP will directly stimulate specific receptors present at the surface of immune cells, called pattern recognition receptors. The activation of these receptors will induce the release of inflammatory mediators. In an attempt to avoid systemic complications of uncontrolled SIRS, the body develops a systemic compensatory anti-inflammatory response syndrome (CARS). CARS induces a post-traumatic immunodepression with a variable duration and amplitude. This immunodepression is physiological, and present in all patients. When immunodepression lasts too long, it becomes pathological, inducing secondary infections (pneumonia mainly), which are the leading cause of complications in ICU. For unknown reasons, some patients will have a rapid immunological recovery, protecting theme from complications. Adequate immunological monitoring could therefore identify patients who recover more slowly and are likely to benefit from an immunomodulatory treatment. At present, the decreased monocytic membrane expression of HLA-DR is the best marker for predicting the occurrence of secondary infections. Several drugs stimulating immunity (GM-CSF, interferon-γ, glucans, immunoglobulins) have been evaluated in patients without immunological monitoring with varying results. Hydrocortisone showed beneficial effects probably by decreasing the amplitude of SIRS. The evaluation of new immune-stimulating treatment, based on pathophysiological data and immunological monitoring (including HLA-DR) now available in most centers, could deeply modify the outcome of severe trauma patients.