Interleukin-12, a key cytokine in Th1-mediated autoimmune diseases

Interleukin 12 (IL-12) is a heterodimeric cytokine produced primarily by antigen-presenting cells (APCs) which plays a key role in promoting type 1 T helper cell (Th1) responses. The powerful activity of IL-12 requires tight control, which is exerted at various levels. Primary control is exerted on IL-12 production by APCs, a major factor driving the response towards the Th1 or Th2 phenotype. Another level of control regulates expression of the IL-12 receptor (IL-12R), which is composed of two subunits, β1 and β2. The IL-12R β2 subunit has signal-transducing capacity and modulation of its expression is central to the regulation of IL-12 responsiveness. Endogenous IL-12 plays an important role in host defense against infection by a variety of intracellular pathogens. Its Th1-promoting activity, however, also favors Th1-mediated immunopathology and, in particular, the induction of Th1-mediated autoimmune diseases. Received 15 January 1999; received after revision 11 March 1999; accepted 16 March 1999