IL-10 Has Differential Effects on the Innate and Adaptive Immune Systems of Septic Patients.
Journal
Journal of immunology (Baltimore, Md. : 1950)
ISSN: 1550-6606
Titre abrégé: J Immunol
Pays: United States
ID NLM: 2985117R
Informations de publication
Date de publication:
15 10 2019
15 10 2019
Historique:
received:
07
06
2019
accepted:
14
08
2019
pubmed:
11
9
2019
medline:
23
5
2020
entrez:
11
9
2019
Statut:
ppublish
Résumé
Sepsis, a disease of divergent pro- and anti-inflammatory-mediated pathways, has a high prevalence of morbidity and mortality, yet an understanding of potential unifying mediators between these pathways that may improve clinical outcomes is largely unclear. IL-10 has classically been designated an immunosuppressive cytokine, although recent data suggest that under certain conditions IL-10 can be immune stimulatory. We sought to further investigate the effect of IL-10 on innate and adaptive immunity in an in vitro human observational cohort study in patients with sepsis via modulation of IL-10 on IFN-γ production by T cells and TNF-α production and HLA-DR expression by monocytes. These results were compared with critically ill nonseptic patients and healthy volunteers. ELISpot analysis was performed using PBMC fraction from patient whole-blood samples. Finally, to provide additional potential clinical relevance, we examined the effect of IL-10 on T cell IFN-γ production in an in vivo cecal ligation and puncture model of sepsis using C57 black/J6 female mice. We found that inhibition of IL-10 significantly increased both production of T cell IFN-γ and monocyte TNF-α, whereas addition of IL-10 increased T cell IFN-γ production but decreased monocyte production of TNF-α and HLA-DR expression. There was no significant effect of IL-10 on control cohorts. IL-10-treated septic mice demonstrated increased IFN-γ production in splenocytes. Thus, IL-10 demonstrates both pro- and anti-inflammatory effects in the septic microenvironment, which is likely cell and context dependent. Further elucidation of relevant signaling pathways may direct future therapeutic targets.
Identifiants
pubmed: 31501258
pii: jimmunol.1900637
doi: 10.4049/jimmunol.1900637
pmc: PMC7206829
mid: NIHMS1575195
doi:
Substances chimiques
IL10 protein, human
0
Interleukin-10
130068-27-8
Interferon-gamma
82115-62-6
Types de publication
Journal Article
Observational Study
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2088-2099Subventions
Organisme : NIGMS NIH HHS
ID : K08 GM129763
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM126928
Pays : United States
Informations de copyright
Copyright © 2019 by The American Association of Immunologists, Inc.
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