Analysis of IL-6, IL-1β and TNF-α production in monocytes isolated from multiple sclerosis patients treated with
Sarah E Fiedler1, Joshua D George1, Haley N Love1
1VA Portland Health Care System, Research and Development Service, 3710 SW US Veterans' Hospital Rd. Portland, OR 97239, USA.
Objective And Design:
The etiology of multiple sclerosis (MS) is unknown, but blood derived monocytes/macrophages are believed to be involved in the pathogenesis through phagocytosis of myelin and production of inflammatory mediators. The objective of this study is to examine inflammatory cytokines that are present at elevated levels in active MS lesions to determine whether there are differences between classically stimulated monocytes isolated from healthy control (HC) and relapsing-remitting MS (RRMS) subjects taking disease modifying drugs (DMDs), including dimethyl fumarate (DMF).
Subjects:
Thirty-nine veterans of the US Armed Forces were enrolled, 21 health controls (HC), and 18 with relapsing-remitting MS (RRMS), all taking DMDs.
Methods:
Use ELISAs to measure production of IL-6, IL-1β and TNF-α by LPS-stimulated peripheral monocytes.
Results:
Activation of monocytes from MS subjects produced significantly more IL-6 than healthy controls (49531 ± 20795 vs 10526 ± 4845), and IL-6 production trended higher in MS subjects taking DMF than those taking other DMDs (72186.9 ± 35156.2 vs 32585.8 ± 17135.4). There were no significant differences in IL-1β or TNF-α secretion.
Conclusions:
Our data suggest that not all DMDs may provide disease modification by suppressing monocyte/macrophage production of pro-inflammatory mediators.
Insights
Multiple sclerosis (MS) patients taking disease-modifying drugs (DMDs) showed higher IL-6 production from monocytes compared to healthy controls. Dimethyl fumarate (DMF) may be less effective at suppressing pro-inflammatory mediators.
Area of Science:
- Neuroimmunology
- Cellular immunology
Background:
- Monocytes/macrophages are implicated in multiple sclerosis (MS) pathogenesis.
- Elevated inflammatory cytokines are observed in active MS lesions.
Purpose of the Study:
- To investigate differences in inflammatory cytokine production by monocytes from healthy controls (HC) and relapsing-remitting MS (RRMS) patients on disease-modifying drugs (DMDs).
- To specifically examine IL-6, IL-1β, and TNF-α levels, including comparisons between patients taking dimethyl fumarate (DMF) and other DMDs.
Main Methods:
- Peripheral blood monocytes were isolated from 39 US military veterans (21 HC, 18 RRMS on DMDs).
- Monocytes were stimulated with LPS, and IL-6, IL-1β, and TNF-α production was measured using ELISAs.
Main Results:
- Monocytes from RRMS patients produced significantly higher levels of IL-6 compared to HC (49531 ± 20795 vs 10526 ± 4845).
- IL-6 production trended higher in RRMS patients taking DMF compared to those on other DMDs (72186.9 ± 35156.2 vs 32585.8 ± 17135.4).
- No significant differences in IL-1β or TNF-α secretion were observed between groups.
Conclusions:
- The findings suggest that not all DMDs may equally suppress pro-inflammatory mediator production by monocytes/macrophages.
- Further research is needed to understand the differential effects of DMDs on immune cell function in MS.
