Analysis of IL-6, IL-1β and TNF-α production in monocytes isolated from multiple sclerosis patients treated with disease modifying drugs.

Abstract

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.