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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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Related in: MedlinePlus

The effect of DMSO in PMN and CD45+ cells in the wrist and ankle joints of KBxN-injected mice.Naïve mice serve as control mice not injected with KBxN serum (n = 3–4).
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pone.0152538.g009: The effect of DMSO in PMN and CD45+ cells in the wrist and ankle joints of KBxN-injected mice.Naïve mice serve as control mice not injected with KBxN serum (n = 3–4).

Mentions: The systemic effect of DMSO was further shown by the significantly (P<0.05) lower wbc numbers, especially monocytes and lymphocytes, in the blood of DMSO-treated mice relative to water-treated mice (Fig 8), regardless of induction of arthritis by K/BxN. A significant decrease in granulocyte content was also observed, albeit only in DMSO-treated naïve mice, and not in K/BxN-injected mice. It should also be noted that the effect of DMSO was specific to wbcs and not to red blood cells or platelets (Fig 8). When the joints were evaluated for the presence of immune cells, it was evident that K/BxN induction promoted recruitment of immune cells to the joints (Fig 9, control versus naïve joints). Interestingly, however, DMSO treatment appeared to reduce the abundance of CD45+ cells and PMN cells in the fore but not the hind joints (Fig 9), which corresponds with DMSO being effective in lowering arthritis-induced swelling in the fore, but not hind paws.


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)

The effect of DMSO in PMN and CD45+ cells in the wrist and ankle joints of KBxN-injected mice.Naïve mice serve as control mice not injected with KBxN serum (n = 3–4).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0152538.g009: The effect of DMSO in PMN and CD45+ cells in the wrist and ankle joints of KBxN-injected mice.Naïve mice serve as control mice not injected with KBxN serum (n = 3–4).
Mentions: The systemic effect of DMSO was further shown by the significantly (P<0.05) lower wbc numbers, especially monocytes and lymphocytes, in the blood of DMSO-treated mice relative to water-treated mice (Fig 8), regardless of induction of arthritis by K/BxN. A significant decrease in granulocyte content was also observed, albeit only in DMSO-treated naïve mice, and not in K/BxN-injected mice. It should also be noted that the effect of DMSO was specific to wbcs and not to red blood cells or platelets (Fig 8). When the joints were evaluated for the presence of immune cells, it was evident that K/BxN induction promoted recruitment of immune cells to the joints (Fig 9, control versus naïve joints). Interestingly, however, DMSO treatment appeared to reduce the abundance of CD45+ cells and PMN cells in the fore but not the hind joints (Fig 9), which corresponds with DMSO being effective in lowering arthritis-induced swelling in the fore, but not hind paws.

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