title: DMSO Represses Inflammatory Cytokine Production from Human Blood Cells and Reduces Autoimmune Arthritis.
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.
authors.affiliation: The Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, B.C., Canada.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Elisia
authors.affiliation: The Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, B.C., Canada.
authors.forename: Hisae
authors.initials: H
authors.lastname: Nakamura
authors.affiliation: The Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, B.C., Canada.
authors.forename: Vivian
authors.initials: V
authors.lastname: Lam
authors.affiliation: The Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, B.C., Canada.
authors.forename: Elyse
authors.initials: E
authors.lastname: Hofs
authors.affiliation: The Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, B.C., Canada.
authors.forename: Rachel
authors.initials: R
authors.lastname: Cederberg
authors.affiliation: The Biomedical Research Centre, University of British Columbia, Vancouver, B.C., Canada.
authors.forename: Jessica
authors.initials: J
authors.lastname: Cait
authors.affiliation: The Biomedical Research Centre, University of British Columbia, Vancouver, B.C., Canada.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Hughes
authors.affiliation: The Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, B.C., Canada.
authors.forename: Leora
authors.initials: L
authors.lastname: Lee
authors.affiliation: The Brain Research Centre, University of British Columbia, Vancouver, B.C., Canada.
authors.forename: William
authors.initials: W
authors.lastname: Jia
authors.affiliation: The Vancouver Prostate Centre at Vancouver General Hospital, Vancouver, B.C., Canada.
authors.forename: Hans H
authors.initials: HH
authors.lastname: Adomat
authors.affiliation: The Vancouver Prostate Centre at Vancouver General Hospital, Vancouver, B.C., Canada.
authors.forename: Emma S
authors.initials: ES
authors.lastname: Guns
authors.affiliation: The Biomedical Research Centre, University of British Columbia, Vancouver, B.C., Canada.
authors.forename: Kelly M
authors.initials: KM
authors.lastname: McNagny
authors.affiliation: The Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, B.C., Canada.
authors.forename: Ismael
authors.initials: I
authors.lastname: Samudio
authors.affiliation: The Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, B.C., Canada.
authors.forename: Gerald
authors.initials: G
authors.lastname: Krystal
mesh_terms: D000818:Animals; D001168:Arthritis / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology*; D001773:Blood Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D018925:Chemokines / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology* / Q000627:therapeutic use; D015232:Dinoprostone / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism; D005260:Female; D018259:Herpesvirus 1, Human / Q000502:physiology; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008297:Male; D008545:Melanoma / Q000188:drug therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D018925:Chemokines; D016207:Cytokines; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D015232:Dinoprostone; D004121:Dimethyl Sulfoxide