A new look at arthritis origins.

People with rheumatoid arthritis generally have hot, swollen, inflamed joints, and this process of inflammation is generally considered to be the root of the disease.

But according to evidence presented this week at the meeting in Anaheim, Calif., of the American Rheumatism Association, and in the May ARTHRITIS AND RHEUMATISM, the inflammation may be secondary to proliferation of the synovial cells lining the joint.

Researchers from World Health Organization arthritis centers at the University of Alabama at Birmingham (UAB) and Mainz, West Germany, have found that, at least in the mouse model they are studying, the earliest change in tissues destined to become arthritic is not inflammation but an uncontrolled reproduction of synovial cells. Using a strain of mice that spontaneously develop arthritis, they observed a "clear-cut dissociation" between tissue destruction and overt inflammation.

"It suggests an alternative mechanism of joint destruction other than classical inflammation," says UAB's William Koopman. "Whether it will hold true [in humans] is speculation."

One factor supporting the theory, Koopman told SCIENCE NEWS, is that anti-inflammatory drugs, while relieving some of the symptoms of rheumatoid arthritis, don't prevent joint destruction.

"There are patients who don't seem to have a lot of inflammation -- their joints are not warm, swollen or tender -- yet there is evidence of joint destruction," notes Koopman.

Hans-Georg Fassbender of the arthritis center in Mainz looked at more than 20,000 tissue biopsies from people diagnosed with rheumatoid arthritis, and found that some of these people had little inflammation. Fassbender's pathological evidence, combined with the clinical evidence of "symptomless" patients, suggests that inflammation is not the whole story in humans as well as in mice.

Comments arthritis expert James Klinenberg of Cedars-Sinai Medical Center in Los Angeles, "We have simplistically said the proliferating [synovial cells] come from an inflammatory stimulus." But a cause-and-effect relationship has never been proved, he notes. The UAB work "is reasonable and exciting -- something to speculate about."

If the problem does prove to be proliferating synovial cells, "It could point the way to the development of agents to interrupt the process," says Koopman. But it also raises a key question: If inflammation doesn't kick off the cell proliferation, what does?

Researchers from the Scripps Clinic and Research Foundation in La Jolla, calif., suggest that one cause may be Epstein-Barr virus, which may stimulate the immune system into marshaling an attack against the body's cartilage and joints.