Abstract
Objective: To assess the impact of etoposide, a topoisomerase II antagonist known to induce monocyte apoptosis, on the development of CIA.
Methods: Mice were primed and booster immunised against collagen II (CII). One group of mice was treated with etoposide two days before CII immunisation and then on four consecutive days weekly until the end of the experiment. The second group of mice was injected with etoposide on four consecutive days a week starting 40 days after CII priming. The third group of mice were controls receiving phosphate buffered saline (PBS). The mice were examined for development of arthritis, numbers of circulating leucocytes, serum CII antibody, and cytokine concentrations.
Results: None of the mice given etoposide before CII immunisation developed arthritis. Serum concentrations of anti-CII antibodies were undetectable in these mice, whereas they displayed significantly increased concentrations of interferon γ and interleukin 6. In addition, the CII specific B cell responses in the draining lymph nodes were highly suppressed. Also, mice treated with etoposide at the onset of clinical arthritis showed reduced frequency of their disease by 50%.
Conclusion: There was a striking disease alleviating impact of topoisomerase II antagonist on the course of CII-induced arthritis.
Full Text
The Full Text of this article is available as a PDF (95.1 KB).
Figure 1 .
Effect of etoposide treatment on arthritis frequency in mice immunised against collagen II. Mice were treated with etoposide two days before immunisation and then four times a week (etoposide pretreated; n=19), or 40 days after immunisation and then four times a week (etoposide treated; n=17), or left untreated (controls; n=17).