Norepinephrine Dysregulates the Immune Response and Compromises Host Defense During Sepsis

American Journal of Respiratory and Critical Care Medicine
Roeland F StolkMatthijs Kox

Abstract

Sepsis is characterized by a dysregulated immune response to infection. Norepinephrine, the cornerstone vasopressor used in septic shock, may contribute to immune dysregulation and impact host defense. To investigate effects of norepinephrine and the alternative vasopressor vasopressin on the immune response and host defense. Leukocytes from 6-9 donors were stimulated in the presence or absence of norepinephrine and vasopressin. One-hundred-and-ninety C57BL/6J mice received continuous infusion of norepinephrine or vasopressin via micro-osmotic pumps and were challenged with lipopolysaccharide or underwent cecal ligation and puncture (CLP). Thirty healthy volunteers were randomized to a 5-hour infusion of norepinephrine, vasopressin or saline, and intravenously challenged with lipopolysaccharide. The relationship between norepinephrine infusion rate and the use of β-blockers, and plasma cytokines was assessed in 195 septic shock patients. Norepinephrine attenuated the production of pro-inflammatory mediators and reactive oxygen species, while augmenting anti-inflammatory interleukin-10 production both in vitro and in lipopolysaccharide-challenged mice. Norepinephrine infusion during CLP resulted in increased bacterial disseminat...Continue Reading

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Nov 4, 2020·Expert Review of Anti-infective Therapy·Nicholas HemingDjillali Annane
Nov 22, 2020·Seminars in Immunopathology·Drashya Sharma, J David Farrar
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Aug 20, 2020·American Journal of Respiratory and Critical Care Medicine·Fabrice Uhel, Tom van der Poll
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NCT02675868

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