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More MS news articles for December 2002

IL-12p35-Deficient Mice Are Susceptible to Experimental Autoimmune Encephalomyelitis: Evidence for Redundancy in the IL-12 System in the Induction of Central Nervous System Autoimmune Demyelination

J Immunol 2002 Dec 15;169(12):7104-10
Gran B, Zhang GX, Yu S, Li J, Chen XH, Ventura ES, Kamoun M, Rostami A.
Departments of. Neurology, Pathology and Laboratory Medicine, and Neurosurgery, University of Pennsylvania School of Medicine, Philadelphia, PA 19104.

Experimental autoimmune encephalomyelitis (EAE) serves as a model for multiple sclerosis and is considered a CD4(+), Th1 cell-mediated autoimmune disease.

IL-12 is a heterodimeric cytokine, composed of a p40 and a p35 subunit, which is thought to play an important role in the development of Th1 cells and can exacerbate EAE.

We induced EAE with myelin oligodendrocyte glycoprotein (MOG) peptide 35-55 (MOG(35-55)) in C57BL/6 mice and found that while IL-12p40-deficient (-/-) mice are resistant to EAE, IL-12p35(-/-) mice are susceptible.

Typical spinal cord mononuclear cell infiltration and demyelination were observed in wild-type and IL-12p35(-/-) mice, whereas IL-12p40(-/-) mice had normal spinal cords.

A Th1-type response to MOG(35-55) was observed in the draining lymph node and the spleen of wild-type mice.

A weaker MOG(35-55)-specific Th1 response was observed in IL-12p35(-/-) mice, with lower production of IFN-gamma.

By contrast, a Th2-type response to MOG(35-55) correlated with disease resistance in IL-12p40(-/-) mice.

Production of TNF-alpha by microglia, CNS-infiltrating macrophages, and CD4(+) T cells was detected in wild-type and IL-12p35(-/-), but not in IL-12p40(-/-), mice.

In addition, NO production was higher in IL-12p35(-/-) and wild-type mice than in IL-12p40(-/-) mice.

These data demonstrate a redundancy of the IL-12 system in the induction of EAE and suggest that p40-related heterodimers, such as the recently cloned IL-23 (p40p19), may play an important role in disease pathogenesis.