Abstract
Early after injury, local tissue damage induces a local and systemic inflammatory response that activates the immune system and leads to the development of systemic inflammatory response syndrome (SIRS). This post-traumatic response often results in uncontrolled release of inflammatory mediators and over-activation of the immune system, which occasionally results in multiple organ dysfunction syndrome (MODS). In parallel, a state of immunosuppression develops. This counter-regulating suppression of different cellular and humoral immune functions has been termed “compensatory anti-inflammatory response syndrome (CARS).” Both SIRS and CARS occur simultaneously even in the initial phase after injury. Pro- and anti-inflammatory cytokines have been suggested to play a major role in development of SIRS, although the degree of involvement of the different cytokines is quite disparate. While TNF-α and IL-1β are quite irrelevant for predicting organ dysfunction, IL-6 is the parameter that best predicts mortality. The hyperinflammatory state seems to be the cause of post-traumatic immunosuppression and heat shock proteins (HSPs), which have been proposed as one of the endogenous stimuli for the deterioration of the immune system acting as danger-associated molecular patterns (DAMPs). Extracellular HSPA1A released from injured tissues increase up to ten times immediately after trauma and even more in patients with MODS. It has powerful immune properties that could contribute to post-traumatic immunosuppression through several mechanisms that have been previously described, so HSPs could represent trauma-associated immunomodulatory mediators. For this reason, HSPA1A has been suggested to be a helpful early prognostic biomarker of trauma after severe injury: serial quantification of serum HSPA1A and anti-Hsp70 concentrations in the first hours after trauma is proposed to be used as a predictive biomarker of MODS and immunosuppression development in polytraumatized patients.
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This work was supported by the Ministry of Economy and Competitiveness ISCIII-FIS grants PI-13/01871, co-financed by ERDF (FEDER) Funds from the European Commission “A way of making Europe.”
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FC designed and performed the study; MCG wrote the manuscript and analyzed and interpreted the data. JV drafted and revised the manuscript. BA and BB assisted with data presentation, drafting, and critical revision of the manuscript. All authors read and approved the final manuscript.
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This study was approved by the Hospital General Universitario “Gregorio Marañón” Clinical Research Ethics Committee. All patients or their direct relatives signed consent prior to inclusion in the study.
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The data appearing in this review are already publicly available in the literature. The datasets that are used and analyzed for the present study are available from the corresponding author upon reasonable request.
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Guisasola, M.C., Alonso, B., Bravo, B. et al. An overview of cytokines and heat shock response in polytraumatized patients. Cell Stress and Chaperones 23, 483–489 (2018). https://doi.org/10.1007/s12192-017-0859-9
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DOI: https://doi.org/10.1007/s12192-017-0859-9