Methylsulfonylmethane (MSM) is an organosulfur compound and the health benefits 
associated with MSM include inflammation. Although MSM has been shown to have 
various physiological effects, no study has yet focused on inflammasome 
activation. The inflammasome is a multiprotein complex that serves as a platform 
for caspase 1-dependent proteolytic maturation and secretion of interleukin-1β 
(IL-1β). In this study, we tested the effect of MSM on inflammasome activation 
using mouse and human macrophages. In our results, MSM significantly attenuated 
NLRP3 inflammasome activation in lipopolysaccharide-primed macrophages, although 
it had no effect on NLCR4 or AIM2 inflammasome activation. Extracts of 
MSM-enriched vegetables presented the same inhibitory effect on NLRP3 
inflammasome activation as MSM. MSM also attenuated the transcriptional 
expression of IL-1α, IL-1β, IL-6, and NLRP3. Taken together, these results show 
that MSM has anti-inflammatory characteristics, interrupts NLRP3 inflammasome 
activation, and inhibits pro-cytokine expression. We further confirmed the 
intracellular mechanism of MSM in relation to NLRP3 inflammasome activation, 
followed by comparison with that of DMSO. Both chemicals showed a synergic 
effect on anti-NLRP3 activation and attenuated production of mitochondrial 
reactive oxygen species (ROS). Thus, MSM is a selective inhibitor of NLRP3 
inflammasome activation and can be developed as a supplement to control several 
metabolic disorders.