Background. Inflammation is associated with strenuous exercise and 
methylsulfonylmethane (MSM) has been shown to have anti-inflammatory properties. 
Methods. Physically active men were supplemented with either placebo or MSM (3 
grams per day) for 28 days before performing 100 repetitions of eccentric knee 
extension exercise. Ex vivo and in vitro testing consisted of evaluating 
cytokine production in blood (whole blood and isolated peripheral blood 
mononuclear cells (PBMCs)) exposed to lipopolysaccharide (LPS), before and 
through 72 hours after exercise, while in vivo testing included the evaluation 
of cytokines before and through 72 hours after exercise. Results. LPS 
stimulation of whole blood after MSM supplementation resulted in decreased 
induction of IL-1β, with no effect on IL-6, TNF-α, or IL-8. After exercise, 
there was a reduced response to LPS in the placebo, but MSM resulted in robust 
release of IL-6 and TNF-α. A small decrease in resting levels of proinflammatory 
cytokines was noted with MSM, while an acute postexercise increase in IL-10 was 
observed with MSM. Conclusion. Strenuous exercise causes a robust inflammatory 
reaction that precludes the cells from efficiently responding to additional 
stimuli. MSM appears to dampen the release of inflammatory molecules in response 
to exercise, resulting in a less incendiary environment, allowing cells to still 
have the capacity to mount an appropriate response to an additional stimulus 
after exercise.