NEW YORK (Reuters Health) - An antibody that induces that apoptosis of activated T cells could represent a useful treatment for rheumatoid arthritis (RA), findings from a recent animal study suggest.
Activated CD4+ T cells are thought to play a role in inflammation and bone destruction, two key features of RA, by recruiting inflammatory cells to the synovial membrane and by inducing osteoclast formation. Therefore, destroying these activated cells could be a useful treatment strategy for RA.
Although anti-Fas monoclonal antibodies have been shown to eliminate these cells, treatment with such antibodies has typically resulted in serious hepatotoxicity. Recently, however, Dr. Masahiko Ohtsuki, from Sankyo Co. Ltd. in Tokyo, and colleagues created an antibody, designated R-125224, that induces apoptosis of activated T cells without harming hepatocytes.
In the new study, reported in the December issue of Arthritis and Rheumatism, Dr. Ohtsuki’s team tested R-125224 in a murine model created to monitor osteoclastogenesis.
Consistent with previous reports, culturing activated CD4+ T cells with peripheral monocytes induced osteoclast formation. Treatment of these T cells with R-125224, however, seemed to suppress osteoclastogenesis.
In the animal model, R-125224 treatment was associated with a reduction in the number of pits formed on implanted dentin slices and with a drop in the number of lymphocytes in the implanted RA synovial tissue.
“Based on the results of our in vitro and in vivo experiments, R-125224-mediated apoptosis of the infiltrated lymphocytes could be a useful therapeutic strategy for RA in terms of suppressing both inflammation and bone destruction,” the researchers state. This novel agent is “considered to be a promising therapeutic candidate for RA,” they add.
Source: Arthritis Rheum 2004;48:3350-3358. [ Google search on this article ]
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