Key Points
IL-10 inhibition increases T cell IFN-γ and monocyte TNF-α in septic patients.
rhIL-10 increases T cell production of IFN-γ in septic patient PBMCs.
rhIL-10 decreases monocyte TNF-α production and HLA-DR expression in sepsis.
Abstract
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.
Footnotes
This work was supported by R35 (Maximizing Investigators' Research Award) GM126928-01 from the National Institute of General Medical Sciences (to R.H.).
The online version of this article contains supplemental material.
- Received June 7, 2019.
- Accepted August 14, 2019.
- Copyright © 2019 by The American Association of Immunologists, Inc.