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Development of Endotoxin Tolerance Does Not Influence the Response to a Challenge with the Mucosal Live-Attenuated Influenza Vaccine in Humans In Vivo

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  • Development of Endotoxin Tolerance Does Not Influence the Response to a Challenge with the Mucosal Live-Attenuated Influenza Vaccine in Humans In Vivo

    Front Immunol. 2017 Dec 11;8:1600. doi: 10.3389/fimmu.2017.01600. eCollection 2017.
    Development of Endotoxin Tolerance Does Not Influence the Response to a Challenge with the Mucosal Live-Attenuated Influenza Vaccine in Humans In Vivo.

    Koch RM1,2, Kox M1,2, Thijs EJM1, Rahamat-Langendoen JC3, van de Veerdonk FL2,4, Gerretsen J1,2, Schloesser J5, Diavatopoulos D6, Rimmelzwaan GF7, Netea MG2,4, van der Hoeven JG1,2, de Jonge MI2,6, Pickkers P1,2.
    Author information

    Abstract

    Introduction:

    The effects of bacterial infections on the response to subsequent viral infections are largely unknown. This is important to elucidate to increase insight into the pathophysiology of bacterial and viral co-infections, and to assess whether bacterial infections may influence the course of viral infections.
    Methods:

    Healthy male subjects received either bacterial endotoxin [Escherichia coli-derived lipopolysaccharide (LPS), 2 ng/kg, n = 15] or placebo (n = 15) intravenously, followed by intranasal Fluenz (live-attenuated influenza vaccine) 1 week later.
    Results:

    LPS administration resulted in increased plasma cytokine levels and development of endotoxin tolerance in vivo and ex vivo, illustrated by attenuated cytokine production upon rechallenge with LPS. Following Fluenz administration, infectivity for the Fluenz A/B strains was similar between the LPS-Fluenz and placebo-Fluenz groups (13/15 subjects in both groups). Also, the Fluenz-induced increase in temperature and IL-6, G-CSF and IP-10 concentrations in nasal wash were similar between both groups.
    Conclusion:

    While endotoxemia profoundly attenuates the immune response upon a second LPS challenge, it does not influence the Fluenz-induced immune response. These results suggest immune suppression after bacterial infection does not alter the response to a subsequent viral infection.


    KEYWORDS:

    Fluenz; endotoxin tolerance; influenza; lipopolysaccharide; live-attenuated quadrivalent influenza vaccine; sepsis; two-hit model

    PMID: 29312282 PMCID: PMC5732479 DOI: 10.3389/fimmu.2017.01600
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