Norepinephrine Dysregulates the Immune Response and Compromises Host Defense during Sepsis.
Am J Respir Crit Care Med
; 202(6): 830-842, 2020 09 15.
Article
em En
| MEDLINE
| ID: mdl-32520577
ABSTRACT
Rationale 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.Objectives:
To investigate effects of norepinephrine and the alternative vasopressor vasopressin on the immune response and host defense.Methods:
Leukocytes from six to nine donors were stimulated in the presence or absence of norepinephrine and vasopressin. A total of 190 C57BL/6J mice received a continuous infusion of norepinephrine or vasopressin via microosmotic pumps and were challenged with LPS or underwent cecal ligation and puncture. Thirty healthy volunteers were randomized to a 5-hour infusion of norepinephrine, vasopressin, or saline and intravenously challenged with LPS. The relationship between the norepinephrine infusion rate and the use of ß-blockers and plasma cytokines was assessed in 195 patients with septic shock.Measurements and MainResults:
Norepinephrine attenuated the production of proinflammatory mediators and reactive oxygen species and augmented antiinflammatory IL-10 production both in vitro and in LPS-challenged mice. Norepinephrine infusion during cecal ligation and puncture resulted in increased bacterial dissemination to the spleen, liver, and blood. In LPS-challenged volunteers, norepinephrine enhanced plasma IL-10 concentrations and attenuated the release of the proinflammatory cytokine IFN-γ-induced protein 10. Vasopressin exerted no immunomodulatory effects across these experimental setups. In patients, higher norepinephrine infusion rates were correlated with a more antiinflammatory cytokine balance, whereas ß-blocker use was associated with a more proinflammatory cytokine balance.Conclusions:
Norepinephrine dysregulates the immune response in mice and humans and compromises host defense. Therefore, it may significantly contribute to sepsis-induced immunoparalysis, whereas vasopressin does not have untoward immunologic effects.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Choque Séptico
/
Vasoconstritores
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Norepinefrina
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Imunidade Ativa
Tipo de estudo:
Clinical_trials
Limite:
Adult
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Aged
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Aged80
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Animals
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Humans
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Male
/
Middle aged
País/Região como assunto:
Europa
Idioma:
En
Revista:
Am J Respir Crit Care Med
Assunto da revista:
TERAPIA INTENSIVA
Ano de publicação:
2020
Tipo de documento:
Article