Total abrogation of collagen II-induced arthritis and the B cell response to type II collagen using suboptimal doses of a topoisomerase II antagonist.
BACKGROUND
Collagen-induced arthritis (CIA) is the most commonly used model of rheumatoid arthritis (RA). In both CIA and RA there is an increase in the cellular content of the synovium, this being dominated by macrophages.


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 gamma 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%.


CONCLUSIONS
There was a striking disease alleviating impact of topoisomerase II antagonist on the course of CII-induced arthritis.
Verdrengh
M
M
Department of Rheumatology, Göteborg University, Göteborg Sweden. margareta.verdrengh@rheuma.gu.se
Jonsson
I-M
IM
Zaether
O
O
Bajtner
E
E
Holmdahl
R
R
Tarkowski
A
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000097:blood; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000517:prevention & control; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology / Q000517:prevention & control; D001402:B-Lymphocytes / Q000276:immunology; D024043:Collagen Type II / Q000276:immunology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005047:Etoposide / Q000627:therapeutic use*; D005260:Female; D007114:Immunization; D007371:Interferon-gamma / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008811:Mice, Inbred DBA; D059005:Topoisomerase II Inhibitors
D000911:Antibodies, Monoclonal; D024043:Collagen Type II; D004791:Enzyme Inhibitors; D015850:Interleukin-6; D059005:Topoisomerase II Inhibitors; D005047:Etoposide; D007371:Interferon-gamma