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
Open accessAbstract
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.
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Monocytes from males produce considerably more inflammatory cytokines than monocytes from females.
“monocytes from males make considerably more inflammatory cytokines as compared to monocytes from females (147).”
From The impact of ageing on monocytes and macrophages (2021) · cites this paper as [147]
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References 53 · Cited by 66
Research works printed but not linked: 2
- Ter Horst R, Jaeger M, Smeekens SP, Oosting M, Swertz MA, Li Y, et al. Host and Environ- mental Factors Influencing Individual Hu- man Cytokine Responses. Cell. 2016 Nov; 167(4): 1111-1124.e13.
- Hotchkiss RS, Monneret G, Payen D. Immu- nosuppression in sepsis: a novel understand- ing of the disorder and a new therapeutic ap- proach. Lancet Infect Dis. 2013 Mar; 13(3): 260-8.
- Authors
- Beenakker, K. G. M., Westendorp, R. G. J., de Craen, A. J. M., Chen, S., Raz, Y., Ballieux, B. E. P. B., Nelissen, R. G. H. H., Later, A. F. L., Huizinga, T. W., Slagboom, P. E., Boomsma, D. I., & Maier, A. B.
- Affiliations
- Leiden University Medical Center (NL)
- University of Copenhagen (DK)
- Vrije Universiteit Amsterdam (NL)
- The Royal Melbourne Hospital (AU)
- ORCID
- Venue
- Journal of Innate Immunity
- Publisher
- S. Karger AG
- Published
- 2019-06-21
- Volume
- 12
- Issue
- 2
- Pages
- 142-153
- ISSN
- 1662-811X (ISSN-L)
- 1662-8128
- PMC
- PMC7098282
- OpenAlex
- W2953366830
- Cited by
- 66
- References
- 53
- Citations by year
- 2026: 12 · 2025: 6 · 2024: 10 · 2023: 6 · 2022: 9 · 2021: 16 · 2020: 7
- FWCI
- 3.19
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of Innate Immunity (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
- Pure Amsterdam UMC (acceptedVersion, cc-by)
- Leiden Repository (Leiden University) (submittedVersion, cc-by-nc-nd)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by-nc)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion, cc-by-nc-nd)
- Funders
- Bristol-Myers Squibb
- Pfizer
- European Commission (FP6 036894)
- Universiteit Leiden (050-060-810, 05040202)
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (050.060.810, NWO 051-14-050, 051-14-050, 05040202)
- Leids Universitair Medisch Centrum
- Stichting Dioraphte
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Sex and Gender in Healthcare
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Keywords
- sex differences, monocytes, cytokine production, lipopolysaccharide, innate immunity, TNF-α, interleukin-6, IL-12, IL-1β, interleukin-1 receptor antagonist, IL-10, interferon-gamma, GM-CSF, sepsis, bacterial infection
- MeSH terms
- Adult, Female, Humans, Lipopolysaccharides, Male, Middle Aged, Monocytes, Sex Characteristics, Monokines
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