THE INTERLEUKIN-12/INTERLEUKIN-12-RECEPTOR SYSTEM: Role in Normal and Pathologic Immune Responses

• Published in: Annual review of immunology 1998-01, Vol.16 (1), p.495-521
• Main Authors: Gately, Maurice K, Renzetti, Louis M, Magram, Jeanne, Stern, Alvin S, Adorini, Luciano, Gubler, Ueli, Presky, David H
• Format: Article
• Language: English
• Subjects: AIDS/HIV; Animals; autoimmune diseases; cytokine; Humans; IL-12; IL-12 receptor; Immunity, Cellular; Interleukin-12 - immunology; Receptors, Interleukin - immunology; Receptors, Interleukin-12; Th subsets; Th1 Cells - immunology; Th2 Cells - immunology
• ISSN: 0732-0582; 1545-3278
• DOI: 10.1146/annurev.immunol.16.1.495

Interleukin-12 (IL-12) is a heterodimeric cytokine that plays a central role in promoting type 1 T helper cell (Th1) responses and, hence, cell-mediated immunity. Its activities are mediated through a high-affinity receptor composed of two subunits, designated β1 and β2. Of these two subunits, β2 is more restricted in its distribution, and regulation of its expression is likely a central mechanism by which IL-12 responsiveness is controlled. Studies with neutralizing anti-IL-12 antibodies and IL-12-deficient mice have suggested that endogenous IL-12 plays an important role in the normal host defense against infection by a variety of intracellular pathogens. However, IL-12 appears also to play a central role in the genesis of some forms of immunopathology. Inhibition of IL-12 synthesis or activity may be beneficial in diseases associated with pathologic Th1 responses, such as multiple sclerosis or Crohn's disease. On the other hand, administration of recombinant IL-12 may have utility in the treatment of diseases associated with pathologic Th2 responses such as allergic disorders and asthma.