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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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(A) The effect of DMSO on melanin production in B16/F10 melanoma cells. *denotes significant difference (P<0.05) in melanin content to non-DMSO treated cells (B) The effect of topical administration of 70% DMSO on the growth of subcutaneously implanted B16/F10 melanoma cells in C57BL/6 mice (n = 8) (C) The effect of DMSO on murine M2 mФ skewing in response to 10 ng/ml IL-4 measured after 72 h of incubation (D) The effect of DMSO in modulating iNOS expression and (E) NO production from M1-skewed murine mФs, measured after 24 h of incubation of cells with 100 ng/mL LPS.
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pone.0152538.g004: (A) The effect of DMSO on melanin production in B16/F10 melanoma cells. *denotes significant difference (P<0.05) in melanin content to non-DMSO treated cells (B) The effect of topical administration of 70% DMSO on the growth of subcutaneously implanted B16/F10 melanoma cells in C57BL/6 mice (n = 8) (C) The effect of DMSO on murine M2 mФ skewing in response to 10 ng/ml IL-4 measured after 72 h of incubation (D) The effect of DMSO in modulating iNOS expression and (E) NO production from M1-skewed murine mФs, measured after 24 h of incubation of cells with 100 ng/mL LPS.

Mentions: DMSO is currently used as an alternative treatment for various cancers. To assess its efficacy as an anti-cancer agent we used the B16 melanoma mouse model since it is both amenable to topical treatment and potentially relevant to treating human cancers topically. Preliminary in vitro studies with these tumor cells demonstrated that DMSO at 1 and 1.5% reduced cell proliferation (data not shown) and, concomitantly, increased the levels of melanin in these cells, in keeping with previous reports that DMSO induces, to some extent, B16 differentiation (Fig 4A) [31].


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)

(A) The effect of DMSO on melanin production in B16/F10 melanoma cells. *denotes significant difference (P<0.05) in melanin content to non-DMSO treated cells (B) The effect of topical administration of 70% DMSO on the growth of subcutaneously implanted B16/F10 melanoma cells in C57BL/6 mice (n = 8) (C) The effect of DMSO on murine M2 mФ skewing in response to 10 ng/ml IL-4 measured after 72 h of incubation (D) The effect of DMSO in modulating iNOS expression and (E) NO production from M1-skewed murine mФs, measured after 24 h of incubation of cells with 100 ng/mL LPS.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0152538.g004: (A) The effect of DMSO on melanin production in B16/F10 melanoma cells. *denotes significant difference (P<0.05) in melanin content to non-DMSO treated cells (B) The effect of topical administration of 70% DMSO on the growth of subcutaneously implanted B16/F10 melanoma cells in C57BL/6 mice (n = 8) (C) The effect of DMSO on murine M2 mФ skewing in response to 10 ng/ml IL-4 measured after 72 h of incubation (D) The effect of DMSO in modulating iNOS expression and (E) NO production from M1-skewed murine mФs, measured after 24 h of incubation of cells with 100 ng/mL LPS.
Mentions: DMSO is currently used as an alternative treatment for various cancers. To assess its efficacy as an anti-cancer agent we used the B16 melanoma mouse model since it is both amenable to topical treatment and potentially relevant to treating human cancers topically. Preliminary in vitro studies with these tumor cells demonstrated that DMSO at 1 and 1.5% reduced cell proliferation (data not shown) and, concomitantly, increased the levels of melanin in these cells, in keeping with previous reports that DMSO induces, to some extent, B16 differentiation (Fig 4A) [31].

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