Dichloroacetate alleviates development of collagen II-induced arthritis in female DBA/1 mice

• Published in: Arthritis research & therapy Vol. 11; no. 5; p. R132
• Main Authors: Bian, Li, Josefsson, Elisabet, Jonsson, Ing-Marie, Verdrengh, Margareta, Ohlsson, Claes, Bokarewa, Maria, Tarkowski, Andrej, Magnusson, Mattias
• Format: Journal Article
• Language: English
• Published: England National Library of Medicine - MEDLINE Abstracts 01.01.2009; BioMed Central Ltd; BioMed Central
• Subjects: Animals; Arthritis, Experimental - immunology; Arthritis, Experimental - pathology; Arthritis, Experimental - prevention & control; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - immunology; Arthritis, Rheumatoid - pathology; Autoantibodies - blood; Autoantibodies - drug effects; Bone Density - drug effects; Collagen - immunology; Dichloroacetic Acid - therapeutic use; Endocrinology and Diabetes; Endokrinologi och diabetes; Estrogens - metabolism; Female; Fysiologi; Hypersensitivity, Delayed - drug therapy; Hypersensitivity, Delayed - immunology; MEDICIN; MEDICINE; Mice; Mice, Inbred DBA; Ovariectomy; Physiology; Research article; Reumatologi och inflammation; Rheumatology and Autoimmunity; T-Lymphocytes - drug effects; TECHNOLOGY; TEKNIKVETENSKAP
• ISSN: 1478-6354; 1478-6362; 1478-6362; 1478-6354
• DOI: 10.1186/ar2799

Dichloroacetate (DCA) has been in clinical use for the treatment of lactacidosis and inherited mitochondrial disorders. It has potent anti-tumor effects both in vivo and in vitro, facilitating apoptosis and inhibiting proliferation. The pro-apoptotic and anti-proliferative properties of DCA prompted us to investigate the effects of this compound in arthritis. In the present study, we used DCA to treat murine collagen type II (CII)-induced arthritis (CIA), an experimental model of rheumatoid arthritis. DBA/1 mice were treated with DCA given in drinking water. Mice treated with DCA displayed much slower onset of CIA and significantly lower severity (P < 0.0001) and much lower frequency (36% in DCA group vs. 86% in control group) of arthritis. Also, cartilage and joint destruction was significantly decreased following DCA treatment (P = 0.005). Moreover, DCA prevented arthritis-induced cortical bone mineral loss. This clinical picture was also reflected by lower levels of anti-CII antibodies in DCA-treated versus control mice, indicating that DCA affected the humoral response. In contrast, DCA had no effect on T cell- or granulocyte-mediated responses. The beneficial effect of DCA was present in female DBA/1 mice only. This was due in part to the effect of estrogen, since ovariectomized mice did not benefit from DCA treatment to the same extent as sham-operated controls (day 30, 38.7% of ovarectomized mice had arthritis vs. only 3.4% in sham-operated group). Our results indicate that DCA delays the onset and alleviates the progression of CIA in an estrogen-dependent manner.