Peptide puts mouse arthritis out of joint.
In rheumatoid arthritis--as in other autoimmune diseases--the immune system remains revved up and damages healthy tissues. Scientists now report that a signaling molecule called vasointestinal peptide, or VIP, can restore order to the immune system in arthritic mice and even reverse arthritis.
While tests of VIP on people are still years away, the compound is attracting attention. In mice, it seems to alter the activities of some immune cells and the amounts of some proteins released into synovial fluid, the viscous liquid that lubricates joints. In so doing, VIP reduces inflammation, cartilage damage, and bone erosion in the animals, the researchers report in the May NATURE MEDICINE.
Although the basic cause of rheumatoid arthritis remains unclear, immune cells known as CD4 helper T cells seem to carry some blame. These immune system workhorses come in two forms dubbed Th1 and Th2. Each makes proteins that play specific roles in guiding an immune response. In arthritic joints, synovial fluid shows signs of too much Th1 activity and too little Th2 activity.
Meanwhile, other immune cells called macrophages contribute their own destructive proteins to the mix.
In earlier studies, VIP had been shown to tone down some Th1 action. To test this inhibition in arthritic tissues, Mario Delgado and his colleagues at Complutense University in Madrid injected mice with an arthritis-inducing mixture of chemicals.
Twelve days after disease onset, the team injected VIP into some mice and left others untreated. The untreated animals didn't improve, but arthritis symptoms lessened in those receiving VIP.
When the scientists examined the chemistry of the animals' synovial fluid, they found that the untreated but not the treated mice show an excess of interferon-gamma. This inflammatory protein is a hallmark of an overzealous Th1 reaction. The treatment also boosted concentrations of the anti-inflammatory protein interleukin-4. Moreover, compared with the other mice, the animals given the VIP treatment had lower concentrations of self-attacking antibodies in their blood and less of an enzyme produced by macrophages that breaks down cartilage.
The researchers don't know precisely how VIP facilitates these changes, but they've identified a receptor on T cells and macrophages to which it binds.
As a person's arthritis worsens, the importance of T cells seems to diminish, while macrophages and certain synovial cells continue to produce harmful chemicals, says Robert P. Kimberly, an immunologist at the University of Alabama, Birmingham School of Medicine. While correcting the Th1-Th2 imbalance may initially be crucial to VIP's effectiveness, keeping macrophages in check could later be more valuable, he says.
Gary S. Firestein, a rheumatologist at the University of California, San Diego School of Medicine in La Jolla, says that although the new study shows that VIP suppresses Th1 activity in these mice, much more research, including toxicity tests, will have to be done before the compound is tried in people.
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|Title Annotation:||indication that vasointestinal peptide can reduce inflamation and damage caused by rheumatoid arthritis|
|Article Type:||Brief Article|
|Date:||May 5, 2001|
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