Galbraith, N. J. , Manek, S., Walker, S., Bishop, C., Carter, J. V., Cahill, M., Gardner, S. A., Polk, H. C. and Galandiuk, S. (2018) The effect of IκK-16 on lipopolysaccharide-induced impaired monocytes. Immunobiology, 223(4-5), pp. 365-373. (doi: 10.1016/j.imbio.2017.10.045) (PMID:29126656)
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Abstract
This study focuses on impaired monocyte function, which occurs in some patients after trauma, major elective surgery, or sepsis. This monocyte impairment increases the risk of secondary infection and death. We aimed to determine the influence IκK-16 had on monocytes using an ex-vivo model of human monocyte impairment. We included the effects of the well-studied comparators interferon-gamma (IFN-γ) and granulocyte-macrophage colony-stimulating factor (GM-CSF) on impaired monocytes. Primary human monocytes were stimulated with 10 ng/mL of lipopolysaccharide (LPS) for 16 h and then challenged with 100 ng/mL LPS to assess the monocyte inflammatory response. Treatment regimens, consisting of either IκK-16, IFN-γ, or GM-CSF, were administered to impaired monocytes near the time of initial LPS stimulation. Stimulation with 10 ng/mL LPS initially promoted a pro-inflammatory response but subsequently impaired production of both tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) and decreased HLA-DR expression. IκK-16 treatment attenuated TNF-α production and programmed death-ligand 1 (PD-L1) expression and increased IL-10 and CD14 expression. IFN-γ treatment increased TNF-α production as well as PD-L1 and HLA-DR expression. In conclusion, limiting early inflammation with IκK-16 suppresses TNF-α production and PD-L1 expression but enhances IL-10 production and preserves CD14 expression for potential future exposure to infective stimuli.
| Item Type: | Articles |
|---|---|
| Additional Information: | This work was funded by the John W. Price and Barbara Thruston Atwood Price Trust, James and Emmeline Ferguson Research Fellowship Trust, and Mary K. Oxley Foundation. |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Galbraith, Dr Norman |
| Authors: | Galbraith, N. J., Manek, S., Walker, S., Bishop, C., Carter, J. V., Cahill, M., Gardner, S. A., Polk, H. C., and Galandiuk, S. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing |
| Journal Name: | Immunobiology |
| Publisher: | Elsevier |
| ISSN: | 0171-2985 |
| Published Online: | 28 October 2017 |
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