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Immune/Allergy Research

The Influence of Methylsulfonylmethane on Inflammation-Associated Cytokine Release before and following Strenuous Exercise.
Van Der Merwe M, Bloomer RJ.

J Sports Med. 2016;2016.

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-1í µí»½, with no effect on IL-6, TNF-í µí»¼, 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-í µí»¼. 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.

MSM enhances LPS-induced inflammatory response after exercise.
Godwin S, Bloomer RJ, Merwe M Van Der, Benjamin R.

J Int Soc Sports Nutr. 2015;12(Suppl 1):P48.

Background: Methylsulfonylmethane (MSM) has been reported to positively influence markers of inflammation and exercise recovery, including decreasing muscle soreness and fatigue. Acute exercise induces tissue damage that results in sterile inflammation that is propagated by secreted mediators such as IL-6 and TNF-a. Regulation of the inflammatory response is critical as chronic inflammation is associated with a plethora of diseases. In addition to the exercise recovery, MSM has also been reported to reduce inflammation associated with osteoarthritis and allergy. Based on these data we designed a pilot study to determine the effect of MSM on Lipopolysaccharide (LPS) - induced inflammatory mediators after a single bout of acute eccentric exercise. Methods: Blood was collected from five recreationally active, healthy men after 28 days of supplementation with MSM (OptiMSM®; Bergstrom Nutrition, Vancouver, WA) or placebo (rice flour) indicated by “Base”. Subjects #19 and #20 received placebo, while #36, #39 and #40 received 3 g of MSM per day. A single bout of acute exercise (10 sets of 10 repetitions of eccentric knee extensions) was performed and additional blood samples were collected immediately (0 h) and 24 h, 48 h and 72 h post exercise. 250 μl of whole blood was plated in a 96-well U bottom plate containing 50 μl of tissue culture media (RPMI1640, antibiotics, 10% FBS) with or without LPS (final concentrations = 0.2 ug/ml). The samples were then incubated at 37°C for 24 h and plasma collected by centrifugation and stored at -80°C until analysis. Plasma cytokine concentrations were determined using a MILLIPLEX MAP human custom cytokine magnetic bead panel that included analytes for IL-1b, IL-6, IL-10, IL-17a and TNF-a. Analytes were quantified using a MAGPIX® and xPONENT software. Results: The supplementation of MSM blunted the increase in the systemic levels of inflammatory cytokines (IL-6 and IL-1b) immediately after exercise. Ex vivo incubation of blood from various time points with LPS, caused a dramatic increase in inflammatory cytokine secretion (IL-6, IL-1b and TNF-a) only after exercise for samples that was exposed to MSM. This response is specific to the stimulation with LPS as secretion of LPS-non responsive proteins is not increased, as evident by the stable levels of IL-17a. There is also a 2-3 fold increase in IL-10 production after LPS stimulation for the MSM group despite having lower IL-10 levels before exercise. Conclusion: MSM is able to reduce the initial cytokine surge that is induced by acute exercise, while allowing for an efficient response to infectious stimuli after a single bout of acute exercise.

A multicentered, open-label trial on the safety and efficacy of methylsulfonylmethane in the treatment of seasonal allergic rhinitis.
Barrager E, Veltmann JR, Schauss AG, Schiller RN.

J Altern Complement Med. 2002;8(2):167-173.

BACKGROUND: Seasonal allergic rhinitis (SAR) affects more than 23 million Americans annually, and current epidemiologic studies indicate that its prevalence within the United States is increasing. Numerous clinical observations and case studies have led researchers to hypothesize that methylsulfonylmethane (MSM) may help ameliorate the symptoms associated with SAR. OBJECTIVE: The primary goal of this study was to evaluate the efficacy of MSM in the reduction of SAR-associated symptoms. This study also examined possible adverse reactions associated with methylsulfonylmethane supplementation. Finally, this study attempted to elucidate the method of action by which MSM elicits its effect on allergy symptoms.
DESIGN: Fifty-five (55) subjects were recruited for the study. All met the criteria for participation in the study. 50 subjects completed the study. Those subjects completing the study consumed 2,600 mg of MSM orally per day for 30 days. Clinical respiratory symptoms and energy levels were evaluated by a Seasonal Allergy Symptom Questionnaire (SASQ) at baseline and on days 7, 14, 21, and 30. Immune and inflammatory reactions were measured by plasma immunoglobulin E (IgE) and C-reactive protein at baseline and on day 30. An additional inflammatory biomarker, plasma histamine, was measured in a subset of subjects (n = 5).
RESULTS: Day 7 upper and total respiratory symptoms were reduced significantly from baseline (p < 0.01 and p < 0.005, respectively). Lower respiratory symptoms were significantly improved from baseline by week 3 (p < 0.001). All respiratory improvements were maintained through the 30-day visit. Energy levels increased significantly by day 14 (p < 0.0001); this increase continued through day 30. No significant changes were observed in plasma IgE or histamine levels. The results of this study are promising. It would be worthwhile to conduct a larger, randomized, double-blind, placebo-controlled study to establish further if MSM would be a useful agent in the treatment of symptoms associated with SAR.
CONCLUSION: The results of this study suggest that MSM supplementation of 2,600 mg/day for 30 days may be efficacious in the reduction of symptoms associated with SAR. Furthermore, few side effects are associated with the use of this compound. Recent acute and subacute chronic toxicologic data on the same source of MSM as used in this study, further validate the safety of this product.

Anti-inflammatory Effect of Methylsulfonylmethane (MSM) in Mice.
Hasegawa T, Ueno S, Kumamoto S, Publishers LS.

Jpn Pharmacol Ther. 2005;33(12).

In this study, we systematically investigated the effect of Methylsulfonylmethane (MSM) on anti-inflammatory properties in mice. The mice models used in our experiments were UVB-irradiated hairless mice for skin damage, ovalbumin-immunized mice for inflammatory cutaneous reaction, and mice injected intradermally with histamine for scratching behavior. We examined MSM's protective effect against skin damage induced by ultraviolet irradiation in hairless mice. The irradiated hairless mice were exposed to UVB (290-320nm) four times a week for 3 weeks, eliciting inflammation of the back skin. It was concluded that the application of MSM ointment helped alleviate the inflammation of the back skin. Next, we examined the effect of MSM administration on the immediate-phase reaction or the late phase reaction in ovalbumin-injected mice. MSM administration suppressed the immediate swelling reaction but not the late-phase reaction in ovalbumin-injected mice. The intradermal injection of histamine induced both scratching behavior and an increase in vascular permeability in ICR mice. Next, we examined the effect of MSM administration on scratching behavior after the intradermal injection of histamine in ICR mice. It was concluded that MSM administration significantly inhibited the scratching behavior caused by histamine. The mechanism underlying the inhibitory effect of scratching behavior by MSM administration remained unclear. However, at least the action of inhibitory scratching behavior is involved with anti-histamine action.

Effects of Oral Dimethyl Sulfoxide and Dimethyl Sulfone on Murine Autoimmune Lymphoproliferative Disease.
Morton JI, Siegel BV.

Proc Soc Exp Biol Med. 1986;183:227-230

The results from several studies examining the effects of DMSO on autoimmune phenomena have been inconclusive, possibly because of differences in experimental models, treatment regimens and doses employed. In the present investigation, autoimmune strain MRL/lpr, C3H/lpr, and male BXSB mice were placed on a continuous treatment regimen with 3% DMSO or 3% DMSO2 in the drinking water, ad libitum, commencing at 1 to 2 months of age, before spontaneous disease development could be detected. This represented doses of 8-10 g/kg/day of DMSO and 6-8 g/kg/day of DMSO2. Both compounds were observed to extend the mean life span of MRL/lpr mice from 5 1/2 months to over 10 months of age. All strains showed decreased antinuclear antibody responses and significant diminution of lymphadenopathy, splenomegaly, and anemia development. Serum IgG levels and spleen IgM antibody plaque formation, however, did not differ from control values. There was no indication of involvement of systemic immunosuppressive or antiproliferative effects, and treated animals were observed to remain healthy and vigorous with no signs of toxicity. These results demonstrate that high doses of both DMSO and its major in vivo metabolite, DMSO2, provide significant protection against the development of murine autoimmune lymphoproliferative disease. Possible mechanisms of protection are discussed.

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