Résumé
Malgré une diminution de la mortalité précoce, le sepsis est aujourd’hui encore responsable d’une mortalité élevée, liée à des séquelles immunologiques, cognitives et neuromusculaires. De nombreux travaux de recherche translationnelle et l’enseignement tiré des échecs des thérapeutiques anti-inflammatoires ont permis d’en dessiner plus clairement la physiopathologie complexe, caractérisée par la coexistence d’une réaction inflammatoire nécessaire à l’élimination de l’agent infectieux mais responsable de lésions tissulaires, et d’une réaction anti-inflammatoire nécessaire à la résolution de l’infection, mais également à l’origine d’une immunodépression profonde et prolongée. La prise en charge plus précoce et intensive du foyer infectieux fait qu’aujourd’hui, en dehors d’une virulence particulière du pathogène ou d’une susceptibilité génétique de l’hôte, les situations où les patients meurent précocement de choc réfractaire lié à une inflammation fulminante sont devenues assez rares. En revanche, une majorité de patients qui survivent aux premières heures du sepsis présentent un état d’immunodépression acquise responsable d’infections nosocomiales et d’une mortalité tardive pouvant atteindre 75 % à cinq ans. L’enjeu des années à venir sera de développer des thérapeutiques ciblées visant à restaurer les capacités immunitaires des patients septiques.
Abstract
Despite a decrease in early mortality, sepsis is still burden with a poor prognosis related to immunological, cognitive and neuromuscular impairments. The lessons learned from the failures of anti-inflammatory therapies and forty years of translational research have led to a better understanding of its complex pathophysiology: Sepsis is characterized by the simultaneous development of an inflammatory response necessary to eliminate the pathogen but responsible for collateral tissue damages, and an anti-inflammatory response required for healing, but also resulting in a profound and prolonged immunosuppression.
Owing to an earlier management of the infection, situations where patients die early from fulminant inflammation and refractory shock have become quite rare, excepted particular pathogen virulence or genetic susceptibility of the host. In contrast, a majority of patients who survive the early hours of sepsis develop an acquired immune deficiency responsible for nosocomial infections and late mortality up to 75% at five years. Development of targeted therapies aiming at restoring immune capacity of septic patients is the ongoing challenge.
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Cet article correspond à la conférence faite par l’auteur au congrès de la SRLF 2015 dans la session : Immunoparalysie au cours du sepsis.
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Uhel, F., Tadié, J.M. & Le Tulzo, Y. Choc septique : mécanismes du décès. Réanimation 24 (Suppl 2), 352–360 (2015). https://doi.org/10.1007/s13546-015-1019-1
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DOI: https://doi.org/10.1007/s13546-015-1019-1