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U of Penn researchers identify gatekeeper involved in chronic inflammatory diseases

PHILADELPHIA The road to many an inflammatory disease is guarded by a cytokine messenger protein called interleukin-27, according to researchers from the University of Pennsylvania School of Veterinary Medicine. Chronic inflammation results when the immune system becomes over stimulated and begins attacking healthy tissue in excess. The Penn researchers found that IL-27 inhibits the immune system cells that are responsible for an array of inflammatory-related diseases, including encephalitis, arthritis, Crohn's disease, lupus and even sepsis.

The findings, which appear online at Nature Immunology, determine that IL-27 may be a useful target for treating a number of such autoimmune diseases. Restoring or augmenting the abilities of IL-27 may be enough to halt inflammation.

"There are many immune-mediated diseases with many different causes, but the type of cells that IL-27 inhibits are a major part of the pathway of cellular signals that lead to inflammation," said Christopher Hunter, professor in Penn Vet's Department of Pathobiology. "Our findings indicate that IL-27 is a prominent factor that helps keep the immune system under control." In previous studies, the researchers found that the IL-27 cytokine limits the duration and intensity of white blood activation, an "off switch" to the cascade of messenger proteins that serve to further activate the immune system. Prior to their research, the general assumption among scientists was that IL-27 promoted inflammation.

To understand the role of IL-27 in chronic inflammation, Hunter and his colleagues at the Ludwig Institute in Melbourne, Amgen and the NIH studied mice engineered to lack the receptor that enables IL-27 to function in normal mice. When infected with the parasite Toxoplasma gondii, which causes toxoplasmosis, the mice developed severe brain inflammation that was caused by helper T cells, a type of white blood cell that activates and directs portions of the immune system.
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Contact: Greg Lester
glester@pobox.upenn.edu
215-573-6604
University of Pennsylvania
21-Aug-2006


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