chapter  23
10 Pages

Interferon-β-1b in inhibits interleukin-12 production in peripheral blood mononuclear cells through an interleukin-10 dependent mechanism

Interleukin-12 (IL-12) is an immunoregulatory cytokine secreted by macrophages, T cells, dendritic cells and microglia. IL-12 is induced by a variety of microbial products and by the interaction of the CD40 ligand on activated T cells with CD40 on antigenpresenting cells (APCs).1-3 IL-12 is secreted in three different forms, a heterodimeric p70, a homodimeric p40 and a monomeric p40. Although p40 is secreted in excess of p70, the latter is primarily responsible for IL-12 biological activities. The p70 heterodimer consists of two subunits, p40 and p35. While p35 is ubiquitously expressed and remains cell associated, p40 expression is highly regulated and its secretion is a better indicator of IL-12 production.3 IL-12 has a number of immunoregulatory effects relevant to the pathogenesis of autoimmune diseases. It is a potent inducer of interferon-γ (IFN-γ) in T cells and natural killer (NK) cells, promotes T-helper type 1 (Th1) responses, and enhances cytotoxic T cell, NK cell and delayed hypersensitivity responses.4-6 IL-12 production is under positive and negative control by Th1 and Th2 cytokines, respectively. IFN-γ enhances, whereas IL-10, IL-4, transforming growth factor-β (TGF-β) and IFN-α/β suppress IL-12 production.3