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DMSO Represses Inflammatory Cytokine Production from Human Blood Cells and Reduces Autoimmune Arthritis.

Elisia I, Nakamura H, Lam V, Hofs E, Cederberg R, Cait J, Hughes MR, Lee L, Jia W, Adomat HH, Guns ES, McNagny KM, Samudio I, Krystal G - PLoS ONE (2016)

Bottom Line: Specifically, we found that between 0.5%-2%, DMSO significantly suppressed the expression of many pro-inflammatory cytokines/chemokines and prostaglandin E2 (PGE2).Although DMSO induces the differentiation of B16/F10 melanoma cells in vitro, topical administration of DMSO to mice subcutaneously implanted with B16 melanoma cells was ineffective at reducing tumor growth, DMSO was also found to block mouse macrophages from polarizing to either an M1- or an M2-phenotype, which may contribute to its inability to slow tumor growth.Topical administration of DMSO, however, significantly mitigated K/BxN serum-induced arthritis in mice, and this was associated with reduced levels of pro-inflammatory cytokines in the joints and white blood cell levels in the blood.

View Article: PubMed Central - PubMed

Affiliation: The Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, B.C., Canada.

ABSTRACT
Dimethyl sulfoxide (DMSO) is currently used as an alternative treatment for various inflammatory conditions as well as for cancer. Despite its widespread use, there is a paucity of data regarding its safety and efficacy as well as its mechanism of action in human cells. Herein, we demonstrate that DMSO has ex-vivo anti-inflammatory activity using Escherichia coli- (E. coli) and herpes simplex virus-1 (HSV-1)-stimulated whole human blood. Specifically, we found that between 0.5%-2%, DMSO significantly suppressed the expression of many pro-inflammatory cytokines/chemokines and prostaglandin E2 (PGE2). However, a significant reduction in monocyte viability was also observed at 2% DMSO, suggesting a narrow window of efficacy. Anti-inflammatory concentrations of DMSO suppressed E. coli-induced ERK1/2, p38, JNK and Akt phosphorylation, suggesting DMSO acts on these signaling pathways to suppress inflammatory cytokine/chemokine production. Although DMSO induces the differentiation of B16/F10 melanoma cells in vitro, topical administration of DMSO to mice subcutaneously implanted with B16 melanoma cells was ineffective at reducing tumor growth, DMSO was also found to block mouse macrophages from polarizing to either an M1- or an M2-phenotype, which may contribute to its inability to slow tumor growth. Topical administration of DMSO, however, significantly mitigated K/BxN serum-induced arthritis in mice, and this was associated with reduced levels of pro-inflammatory cytokines in the joints and white blood cell levels in the blood. Thus, while we cannot confirm the efficacy of DMSO as an anti-cancer agent, the use of DMSO in arthritis warrants further investigation to ascertain its therapeutic potential.

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DMSO levels in (A) hind and fore joints and (B) plasma of K/BxN mice.* denotes significant (P<0.05) difference between control (n = 7) and DMSO-treated mice (n = 9).
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pone.0152538.g007: DMSO levels in (A) hind and fore joints and (B) plasma of K/BxN mice.* denotes significant (P<0.05) difference between control (n = 7) and DMSO-treated mice (n = 9).

Mentions: The ability of DMSO to significantly reduce arthritis-induced swelling in the front, but not in the hind paws corresponded with the efficacy of DMSO to modulate the gene expression of several pro-inflammatory cytokines that have been implicated in arthritic events (Fig 6). For example, gene expression levels of IL-1β, IL-6, TNFα, CXCL1 and CXCL2 in the hind paws of the DMSO-treated mice were not significantly different from the hind paws of water-treated mice while the fore paws of the DMSO-treated mice expressed significantly (P<0.05) lower levels of pro-inflammatory genes (IL-1β, IL-6, CXCL1 and CXCL2) than the fore paws of mice in the control group. DMSO levels in the joints and plasma of the mice were also quantified. Interestingly, even though DMSO was topically administered to only the hind paws, similar DMSO concentrations were detected in both the fore and hind joints as well as in the plasma of the mice (Fig 7). These results suggest that DMSO diffuses systemically throughout the body.


DMSO Represses Inflammatory Cytokine Production from Human Blood Cells and Reduces Autoimmune Arthritis.

Elisia I, Nakamura H, Lam V, Hofs E, Cederberg R, Cait J, Hughes MR, Lee L, Jia W, Adomat HH, Guns ES, McNagny KM, Samudio I, Krystal G - PLoS ONE (2016)

DMSO levels in (A) hind and fore joints and (B) plasma of K/BxN mice.* denotes significant (P<0.05) difference between control (n = 7) and DMSO-treated mice (n = 9).
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4816398&req=5

pone.0152538.g007: DMSO levels in (A) hind and fore joints and (B) plasma of K/BxN mice.* denotes significant (P<0.05) difference between control (n = 7) and DMSO-treated mice (n = 9).
Mentions: The ability of DMSO to significantly reduce arthritis-induced swelling in the front, but not in the hind paws corresponded with the efficacy of DMSO to modulate the gene expression of several pro-inflammatory cytokines that have been implicated in arthritic events (Fig 6). For example, gene expression levels of IL-1β, IL-6, TNFα, CXCL1 and CXCL2 in the hind paws of the DMSO-treated mice were not significantly different from the hind paws of water-treated mice while the fore paws of the DMSO-treated mice expressed significantly (P<0.05) lower levels of pro-inflammatory genes (IL-1β, IL-6, CXCL1 and CXCL2) than the fore paws of mice in the control group. DMSO levels in the joints and plasma of the mice were also quantified. Interestingly, even though DMSO was topically administered to only the hind paws, similar DMSO concentrations were detected in both the fore and hind joints as well as in the plasma of the mice (Fig 7). These results suggest that DMSO diffuses systemically throughout the body.

Bottom Line: Specifically, we found that between 0.5%-2%, DMSO significantly suppressed the expression of many pro-inflammatory cytokines/chemokines and prostaglandin E2 (PGE2).Although DMSO induces the differentiation of B16/F10 melanoma cells in vitro, topical administration of DMSO to mice subcutaneously implanted with B16 melanoma cells was ineffective at reducing tumor growth, DMSO was also found to block mouse macrophages from polarizing to either an M1- or an M2-phenotype, which may contribute to its inability to slow tumor growth.Topical administration of DMSO, however, significantly mitigated K/BxN serum-induced arthritis in mice, and this was associated with reduced levels of pro-inflammatory cytokines in the joints and white blood cell levels in the blood.

View Article: PubMed Central - PubMed

Affiliation: The Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, B.C., Canada.

ABSTRACT
Dimethyl sulfoxide (DMSO) is currently used as an alternative treatment for various inflammatory conditions as well as for cancer. Despite its widespread use, there is a paucity of data regarding its safety and efficacy as well as its mechanism of action in human cells. Herein, we demonstrate that DMSO has ex-vivo anti-inflammatory activity using Escherichia coli- (E. coli) and herpes simplex virus-1 (HSV-1)-stimulated whole human blood. Specifically, we found that between 0.5%-2%, DMSO significantly suppressed the expression of many pro-inflammatory cytokines/chemokines and prostaglandin E2 (PGE2). However, a significant reduction in monocyte viability was also observed at 2% DMSO, suggesting a narrow window of efficacy. Anti-inflammatory concentrations of DMSO suppressed E. coli-induced ERK1/2, p38, JNK and Akt phosphorylation, suggesting DMSO acts on these signaling pathways to suppress inflammatory cytokine/chemokine production. Although DMSO induces the differentiation of B16/F10 melanoma cells in vitro, topical administration of DMSO to mice subcutaneously implanted with B16 melanoma cells was ineffective at reducing tumor growth, DMSO was also found to block mouse macrophages from polarizing to either an M1- or an M2-phenotype, which may contribute to its inability to slow tumor growth. Topical administration of DMSO, however, significantly mitigated K/BxN serum-induced arthritis in mice, and this was associated with reduced levels of pro-inflammatory cytokines in the joints and white blood cell levels in the blood. Thus, while we cannot confirm the efficacy of DMSO as an anti-cancer agent, the use of DMSO in arthritis warrants further investigation to ascertain its therapeutic potential.

Show MeSH
Related in: MedlinePlus