Antibody slows progression of RA in animal model

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Antibody slows progression of rheumatoid arthritis in animal model

http://www.arthritiswebsite.com/news/news_detail.jsp?news_id=959682336703-61315

WESTPORT, May 29 (Reuters Health) - The same anti-CD40 antibodies that

have been used to boost the immune system's response to infection or to

fight cancer can also be used to dampen the autoimmune inflammatory

processes that underlie the progression of rheumatoid arthritis (RA).

This apparent paradox of the function of agonistic anti-CD40 antibodies

might be explained by the timing of the administration of the

antibodies, Dr. Marco Londei, and colleagues at the Imperial College

School of Medicine, in London, UK, speculate in the June issue of Nature

Medicine.

The scientists examined the effects of the anti-CD40 antibodies in a

mouse model of chronic collagen-induced RA. They injected the mice with

monoclonal anti-CD40 antibodies daily for 10 days beginning on the day

of disease onset. They continued the injections every other day for the

duration of the experiment.

Anti-CD40 antibodies were " very efficient in controlling the long-term

evolution of disease, " Dr. Londei's group reports. Specifically, the

injections resulted in reduced clinical scores and paw thickness for up

to 40 days after the onset of disease. " Although complex events are

likely to be involved in the therapeutic action of monoclonal antibodies

against CD40, a constant feature here was the downregulation of

production of [interferon gamma], the hallmark of pathogenic T

lymphocytes in autoimmunity, " the authors write. This effect was

paralleled by an upregulation of interleukin 10, as well as an increase

in the production of interleukin 4.

Given the paradoxical effects of anti-CD40 antibodies in treating

infection and cancer, Dr. Londei's team find that these new results are

" unexpected. " They suspect that the timing of antibody administration

may determine the nature of the effect, since " the administration of

monoclonal antibody against CD40 before immunization does not produce

the same functional outcome as administration after antigenic

challenge. "

" Eventually, this knowledge could be used for the development of new

therapeutic strategies to fight immune attack of otherwise healthy

tissues, " Drs. E. Zanelli and R. E. M. Toes, of Leiden University

Medical Center, in the Netherlands, comment in an accompanying

editorial.

Nat Med 2000;6:629-630,673-679. -Westport Newsroom 203 319 2700