Research article

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

Li Bian¹ , Elisabet Josefsson¹ , Ing-Marie Jonsson¹ , Margareta Verdrengh¹ , Claes Ohlsson² , Maria Bokarewa¹ , Andrej Tarkowski^{^} and Mattias Magnusson¹

¹  Department of Rheumatology and Inflammation Research, Sahlgrenska Academy, University of Gothenburg, Guldhedsgatan 10A, Box 480, SE-405 30, Gothenburg, Sweden

²  Centre for Bone Research, Department of Internal Medicine, Sahlgrenska University Hospital, Gröna Stråket 8, SE-413 45, Gothenburg, Sweden

author email corresponding author email^Deceased

Arthritis Research & Therapy 2009, 11:R132doi:10.1186/ar2799

Published:	1 September 2009

Abstract

Introduction

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.

Methods

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.

Results

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).

Conclusion

Our results indicate that DCA delays the onset and alleviates the progression of CIA in an estrogen-dependent manner.