Men Have a Stronger Monocyte-Derived Cytokine Production Response upon Stimulation with the Gram-Negative Stimulus Lipopolysaccharide than Women: A Pooled Analysis Including 15 Study Populations

Karel G M Beenakker, Rudi G J Westendorp, Anton J M de Craen, Sijia Chen, Yotam Raz, Bart E P B Ballieux, Rob G H H Nelissen, Alexander F L Later, Tom W Huizinga, Pieternella E Slagboom, Dorret I Boomsma, Andrea B Maier

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

The incidence of bacterial infections and sepsis, as well as the mortality risk from sepsis, is sex specific. These clinical findings have been attributed to sex differences in immune responsiveness. The aim of the present study was to investigate sex differences in monocyte-derived cytokine production response upon stimulation with the gram-negative stimulus lipopolysaccharide (LPS) using cytokine data from 15 study populations. Individual data on ex vivo cytokine production response upon stimulation with LPS in whole blood were available for 4,020 subjects originating from these 15 study populations, either from the general population or from patient populations with specific diseases. Men had a stronger cytokine production response than women to LPS for tumour necrosis factor-α, interleukin (IL)-6, IL-12, IL-1β, IL-1RA, and IL-10, but not for interferon-γ. The granulocyte-macrophage colony-stimulating factor production response was lower in men than in women. These sex differences were independent of chronological age. As men had higher monocyte concentrations, we normalized the cytokine production responses for monocyte concentration. After normalization, the sex differences in cytokine production response to LPS disappeared, except for IL-10, for which the production response was lower in men than in women. A sex-based approach to interpreting immune responsiveness is crucial.

Original languageEnglish
Pages (from-to)1-12
Number of pages12
JournalJournal of innate immunity
Volume12
Issue number2
Early online date21 Jun 2019
DOIs
Publication statusPublished - 2020
Externally publishedYes

Bibliographical note

© 2019 The Author(s) Published by S. Karger AG, Basel.

Funding

This study was funded by an unrestricted grant from the Board of Leiden University Medical Center. The included studies were funded by the Seventh Framework Programme MYOAGE, HEALTH-2007-2.4.5-10 (Myoage young study and Myoage old study); the Prof. Dr. Kassenaar Fund and the Praeventiefonds, M.28-2293 (Meningitis relatives study); the Dutch Society for Support of Research into Multiple Sclerosis, 96-229 MS (MS-SLE relatives and MS-SLE); the Netherlands Foundation for the Advancements of Tropical Research, WOTRO 93-467, Stichting Dioraphte, and the Netherlands Organization for Scientific Research, NWO 051-14-050 (Ghana study); the European Union-funded Network of Excellence LifeSpan, FP6 036894 (Ghana study, Leiden 85-plus study); the Netherlands Genomics/Netherlands Organization for Scientific Research, NGI/NWO, 05040202 and 050-060-810 NCHA (LLS and Leiden 85-plus study); Bristol-Myers Squibb, USA (PROSPER study); the Dutch College for Health Insurance Companies and Centocor and Schering-Plough (BEST); and Pfizer Inc., Groton, CT, USA (GARP study).

FundersFunder number
BEST
Board of Leiden University Medical Center
Dutch College for Health Insurance Companies and Centocor and Schering-Plough
Dutch Society for Support of Research into Multiple Sclerosis
European Union-funded Network of Excellence LifespanFP6 036894
NCHA
NGI/NWO05040202, 050-060-810
Netherlands Foundation for the Advancements of Tropical ResearchWOTRO 93-467
Netherlands Organization for Scientific ResearchNWO 051-14-050
Bristol-Myers Squibb
Pfizer
Seventh Framework ProgrammeHEALTH-2007-2.4.5-10
Stichting Dioraphte

    Keywords

    • Blood
    • Cytokines
    • Gender
    • Innate immunity
    • Lipopolysaccharide
    • Sex

    Cohort Studies

    • Netherlands Twin Register (NTR)

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