Mechanisms of Dimethyl Sulfoxide Augmentation of IL-1β Production

Abstract

Expression of the inflammatory cytokine IL-1β occurs in various inflammatory diseases, and IL-1β production is regulated at multiple levels. There are conflicting reports about the effects of antioxidants on IL-1β production. In this study, we investigated the regulatory role of the antioxidant DMSO on LPS-stimulated IL-1β gene expression in human PBMC and in vivo. This study demonstrated that 1% DMSO increased LPS-stimulated (50 ng/ml) IL-1β secretion in a dose- and time-dependent manner without altering TNF or IL-6. DMSO also elevated IL-1β secretion by PBMC in response to exogenous superoxide anions. Despite the increase in IL-1β, there was no augmentation of NF-κB with the addition of DMSO. The steady state mRNA coding for IL-1β following LPS stimulation was also increased. Cycloheximide studies demonstrated that the DMSO augmentation of IL-1β mRNA did not require de novo protein synthesis, and studies with actinomycin D showed that DMSO did not alter the half-life of IL-1β mRNA, suggesting that DMSO did not change the stability of IL-1β mRNA. Experiments using a reporter vector containing the 5′-flanking region of the human IL-1β gene revealed that DMSO augmented LPS-induced IL-1β reporter activity. In vivo, treatment of mice with DMSO significantly increased plasma levels of IL-1β after endotoxin challenge. These data indicate that DMSO directly increases LPS-stimulated IL-1β protein production through the mechanisms of augmenting promoter activity and increasing mRNA levels.

Lipopolysaccharide inhibits myogenic differentiation of C2C12 myoblasts through the Toll-like receptor 4-nuclear factor-κB signaling pathway and myoblast-derived tumor necrosis factor-α

“…We acknowledge that a DMSO vehicle control was not included in two experiments shown in Figs 5 and 6. High concentrations of DMSO (1–2% [vol/vol]) have been shown to augment the LPS effect on immune cells (i.e., increase inflammatory cytokine secretion) [90]; therefore, in our study, the relative effect of TAK-242 on the LPS response may have been weakened. Nevertheless, previous studies have shown that, even at concentrations as high as 1–2% (vol/vol), DMSO has no effect on NF-κB activity in various cell lines, reducing this concern [90–92].…”

Dimethyl sulphoxide and dimethyl sulphone are potent inhibitors of IL-6 and IL-8 expression in the human chondrocyte cell line C-28/I2

“…DMSO possesses anti-inflammatory properties (Melchior et al, 2003), as well as the ability to act as a free radical scavenger (Xing and Remick, 2005). Thus, its properties have been exploited in the treatment of dermatological, rheumatic and renal manifestations of amyloidosis.…”

Dimethyl sulfoxide as an inducer of differentiation in preosteoblast MC3T3‐E1 cells

“…DMSO possesses anti-inflammatory properties [4], as well as the ability to act as a free radical scavenger [5]. Thus, its properties have been exploited in the treatment of dermatological, rheumatic, and renal manifestations of amyloidosis.…”