News Media Home | Hopkins Medicine Home
December 18, 2001
MEDIA CONTACT: Joanna Downer
PHONE: 410-614-5105
E-MAIL: jdowner1@jhmi.edu
Suppressing Entire Immune System Unlikely to Be Best Way To Treat Autoimmune Diseases, New Findings Show
Suppressing the immune system is one way to treat autoimmune diseases, frustrating conditions in which the body's tissues are attacked by "friendly fire." But a new study shows that such blanket defenses are probably not the best way, say scientists from The Johns Hopkins University School of Medicine.
One of the immune system's soldiers, interferon-gamma, actually helps prevent
tissue damage in mice given a condition similar to a heart-damaging autoimmune
disease in humans, the scientists report in the Dec. 18 issue of the journal
Circulation.
"In treating autoimmune disease," says Noel Rose, M.D., Ph.D., a professor
of pathology at Hopkins, "it's possible that treatments that alter the
immune system's overall function could make one autoimmune disease better but
make a second one worse."
The scientists discovered interferon-gamma's protective role as they were trying
to figure out how an immune soldier called interleukin-12 causes heart damage
in this disease, known as myocarditis. Because interleukin-12 "recruits"
interferon-gamma, increasing its presence in cells, the scientists suspected
interferon-gamma might be involved in damaging tissue.
Unexpectedly, mice without normal interferon-gamma function had more heart
damage, and mice treated with extra interferon-gamma had less damage than normal
mice. Extra interferon-gamma prevented heart damage completely in seven of the
11 mice studied, says Rose, whose studies were funded by the National Institutes
of Health.
"Scientists generally thought that interferon-gamma was responsible for
many actions of interleukin-12, so it was surprising that the two proteins really
have opposite effects in these mice," explains Marina Afanasyeva, M.D.,
M.P.H., a Ph.D. candidate in molecular microbiology and immunology at Johns
Hopkins University's Bloomberg School of Public Health. "Interleukin-12
probably depends on interferon-gamma for its effects in some circumstances but
not others."
Many autoimmune diseases are poorly understood, says Rose, but some are linked
to viral infections. Treating these diseases can be frustrating, as opportunistic
autoimmune diseases -- those that rise from the ashes of another -- are frequently
seen, he adds.
Critical to the scientists' discovery was their mouse model of autoimmune myocarditis,
which in humans stems from infection with the Coxackievirus. While most people
shake off the infection's flu-like symptoms, for reasons still unknown at least
50,000 people per year subsequently develop an errant, long-lasting autoimmune
reaction that damages the heart muscle.
The Hopkins team had already identified the target of this immune attack as
a protein called cardiac myosin. By injecting mice with excess cardiac myosin,
they created the autoimmune response and heart damage without using the virus.
Because interleukin-12 was already a primary suspect in this autoimmune process
and it stimulates production of interferon-gamma, the scientists thought interferon-gamma
might be responsible for its damaging effects.
However, mice whose gene for interferon-gamma was knocked out and mice whose
interferon-gamma protein was blocked with an antibody both had larger hearts
and more physical evidence of heart tissue inflammation than mice with normally
functioning interferon-gamma, says Afanasyeva. They're still evaluating the
effects on heart function, she adds, and they don't yet know whether interferon-gamma
actively protects the heart or its absence allows another as-yet-unknown damaging
activity to emerge.
Despite its apparent protective role in myocarditis, interferon-gamma is unlikely to be useful as a treatment, notes Rose. "Interferon-gamma is a very potent agent but it can also be toxic," adds Afanasyeva. "If we study more how interferon-gamma acts, perhaps we can design safer agents that mimic it."
The scientists emphasize that different auto-immune diseases likely have different "good" and "bad" soldiers. Even though it is protective in myocarditis, for example, interferon-gamma is known to make multiple sclerosis worse.
Co-authors are Yan Wang, Ziya Kaya (supported by a fellowship from the Deutsche Herzstiftung e.V.), Elizabeth Stafford and Malte Dohmen, of the department of pathology at the Johns Hopkins School of Medicine; and Amir Sadighi Akha, now in the pathology department at the University of Michigan Medical School.
Related Web site:
http://circ.ahajournals.org