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The Dysregulated Host Response

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Management of Dysregulated Immune Response in the Critically Ill

Part of the book series: Lessons from the ICU ((LEICU))

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Abstract

This chapter focuses on immune response as part of “host response to severe infection” describing the time evolution of immune phenotype from hyper-inflammation to immunodepression. These phenotypes allow to consider different phases with different genetic, transcriptomic, proteomic, and functional patterns. The chapter describes the multiple factor modifications and highlights the role of the shift in cell metabolism. This shift results mainly from glucose metabolism shift towards aerobic glycolysis after immune cell stimulation. The key role of HIF-1α and mTOR is depicted to increase the rate of glucose consumption in aerobic glycolysis, with an activation of intermediate pathways as the pentose phosphate pathway and pyruvate transformation. Elevated pyruvate production associated with abnormal function of the tricarboxylic acid and mitochondrial oxidative phosphorylation to produce ATP stimulates lactate production and lipid synthesis. The impact of the context (comorbidities, chronic treatments, genetic predisposition) may largely influence the tolerance of the described phenotypic changes. The integrated view then helps to propose new therapeutic axes based on metabolic pathway modifications, as metformin or HIF-1α inhibitor.

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Author information

Authors and Affiliations

  1. Université Paris 7, Denis Diderot, UFR de Médecine, Sorbonne Cité, Paris, France

    D. Payen

  2. CHU de Nice, France and INSERM U1065, C3M, Université Côte d’Azur, Nice, France

    M. Carles

  3. Université de Nice, Laboratoire d’Immunologieet Service de Néphrologie-Dialyse-Transplantation CHU de Nice, Université Côte d’Azur, Nice, France

    B. Seitz-Polski

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  1. D. Payen
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  2. M. Carles
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Editors and Affiliations

  1. Department of Anaesthesiology and Intensive Therapy, Semmelweis University, Budapest, Hungary

    Zsolt Molnar

  2. Department of Critical Care, King’s College London, Guy’s & St Thomas’ NHS Foundation Trust, London, UK

    Marlies Ostermann

  3. The Queen’s Medical Research Institute Edinburgh BioQuarter, Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK

    Manu Shankar-Hari

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Payen, D., Carles, M., Seitz-Polski, B. (2023). The Dysregulated Host Response. In: Molnar, Z., Ostermann, M., Shankar-Hari, M. (eds) Management of Dysregulated Immune Response in the Critically Ill. Lessons from the ICU. Springer, Cham. https://doi.org/10.1007/978-3-031-17572-5_2

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  • DOI: https://doi.org/10.1007/978-3-031-17572-5_2

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