Histamine and inflammation in RA patients (NEW DISCOVERY)

[Mike Bartolatz]

Unexpected Discovery Made By Scientists Exploring Inflammation In RA
20 Feb 2006
http://www.medicalnewstoday.com/medical ... wsid=37884#

What makes joints in people with rheumatoid arthritis, and related
conditions like Lyme disease or lupus, so susceptible to attack by the
body's immune system, leading to painful flare-ups and deterioration? The
answer may surprise you.

The answer did surprise investigators at Joslin Diabetes Center and
Massachusetts General Hospital (MGH) in Boston, who gained a novel insight
into this question in a recent collaborative study. Their report appeared in
the January 29 online issue of Nature Immunology, and is scheduled to appear
in the February print edition.

Working with an animal model of rheumatoid arthritis, the researchers
discovered that histamine, a small molecule usually associated with asthma
and allergy, is produced as part of the inflammatory process during the
development of arthritis. Histamine made the blood vessels surrounding the
joints especially vulnerable to leakage, and thereby rendered the joints
more susceptible to inflammatory attack. The researchers believe that this
is true not only in rheumatoid arthritis, but perhaps also in other
autoimmune conditions with which arthritis is associated, such as lupus, and
in some infectious diseases, like Lyme disease.

"For patients with rheumatoid arthritis, these new findings raise the
possibility that medications designed to prevent the blood vessels from
becoming leaky might one day be used to delay the onset of arthritis or to
prevent flare-ups of disease," said Christophe Benoist, M.D., Ph.D., who led
the study together with Diane Mathis, Ph.D., and Ralph Weissleder, M.D.,
Ph.D. Drs. Mathis and Benoist head Joslin?s Section on Immunology and
Immunogenetics, hold the William T. Young Chair in Diabetes Research at
Joslin, and are Professors of Medicine at Harvard Medical School. Dr.
Weissleder heads the Center for Molecular Imaging Research at MGH and is a
Professor of Radiology at Harvard Medical School.

While the Joslin lab focuses its work on type 1 diabetes, arthritis has
several related mechanisms. Like type 1 diabetes, rheumatoid arthritis is an
autoimmune disease, in which the body's immune system attacks itself as
though fighting off an enemy invader.

The Arthritis Foundation reports the number of Americans with arthritis or
chronic joint symptoms has risen from 35 million to 66 million (nearly 1 in
3 adults) in 2005. Rheumatoid arthritis (RA) is a chronic autoimmune disease
characterized by inflammation of the lining, or synovium, of the joints. It
is one of the most severe forms of arthritis and can lead to long-term joint
damage, resulting in chronic pain, loss of function and disability. RA
affects 1 percent of the U.S. population or 2.1 million Americans, mostly
women.

In their study, the researchers developed a new microscopic imaging method
to visualize changes in blood vessel permeability in anesthetized mice.
Within minutes following the delivery of arthritis-causing antibodies to the
mice, the blood vessels around the joints became temporarily leaky, making
it easier for the antibodies to enter the joint spaces. There, the
antibodies set off a cascade of inflammatory cells and molecules, eventually
resulting in arthritis.

"The big surprise was that the other blood vessels throughout the body did
not become leaky, suggesting that there is something special about the
vessels in the joints," says Bryce Binstadt, M.D., Ph.D., of Joslin and
Children's Hospital Boston, lead author on the study.

In trying to identify the special feature, the investigators made the even
more unexpected discovery that histamine was responsible for the joint blood
vessel leakiness -- in fact, the researchers could mimic the effect of the
antibodies on blood vessel leakiness by just injecting histamine.

Other researchers participating in the study included Pratik R. Patel,
Herlen Alencar, M.D., and Umar Mahmood, M.D., Ph.D., of the Center for
Molecular Imaging Research, Massachusetts General Hospital; Peter A.
Nigrovic, M.D., of Children's Hospital and Brigham and Women?s Hospital,
Boston; and David M. Lee, M.D., Ph.D., of Brigham and Women's Hospital.

This work was funded by grants from the National Institutes of Health. Dr.
Binstadt is supported by a Pfizer Postdoctoral Fellowship in
Rheumatology/Immunology.

To view this press release online, which includes an image related to this
study, click on the following link: http://www.joslin.org/1083_3262.asp