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Suppressing entire immune system unlikely to be best way to treat autoimmune diseases, new findings show

thers."

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
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Contact: Joanna Downer
jdowner1@jhmi.edu
410-614-5105
Johns Hopkins Medical Institutions
18-Dec-2001


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