ITEMS

modern scholarly publishers in the finest tradition

Journals

	Search

Critical Reviews™ in Immunology

ISSN for PRINT: 1040-8401

Institutional price:	$831.00
Issues per year:	6

Best Paper Award Selection - Editorial Board Site

2004, Volume24

75 pages

DOI: 10.1615/CritRevImmunol.v24.i2

Issue price - $132.00

Role of the IL-12/IL-23 System in the Regulation of T-Cell Responses in Central Nervous System Inflammatory Demyelination

Bruno Gran
Department of Neurology, Thomas Jefferson University, 300 Jefferson Hospital for Neuroscience, 900 Walnut Street, Philadelphia, PA 19107

Guang-Xian Zhang
Department of Neurology, Thomas Jefferson University, 300 Jefferson Hospital for Neuroscience, 900 Walnut Street, Philadelphia, PA 19107

Abdolmohamad Rostami
Department of Neurology, Thomas Jefferson University, 300 Jefferson Hospital for Neuroscience, 900 Walnut Street, Philadelphia, PA 19107

ABSTRACT

Interleukin-12 (IL-12) has long been considered essential in T-cell-mediated autoimmune diseases, including multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). This is based on the strong capacity of IL-12 to induce T-cell activation and Th1 differentiation. However, recent data have shown that the perceived central role of IL-12 in CNS inflammatory demyelination is actually due to IL-23, a closely related cytokine sharing the p40 subunit and the β1 receptor chain with IL-12. There appear to be three different aspects of IL-12 involvement in EAE: (1) disease-promoting effects of exogenous IL-12, particularly in relapsing—remitting EAE and adoptive transfer EAE; (2) lack of IL-12 requirement in EAE pathogenesis, as indicated by studies in knockout mice; and (3) immunoregulatory effects of IL-12. Together, these observations make IL-12 a less attractive target for therapeutic intervention in MS. IL-23 neutralization may be a better candidate for therapeutic intervention, and it remains to be established whether blocking IL-23 with antibodies in adult mice will have the same effects as knocking out the IL-23p19 gene. Current clinical trials of neutralizing anti— IL-12 antibodies in other immune-mediated diseases target the p40 subunit, thereby neutralizing both IL-12 and IL-23. Thus, new experimental data are expected to have important implications for therapy of human diseases.