Regulatory mechanisms and their therapeutic implications of interleukin-12 production in immune cells.

Studies with neutralizing anti-interleukin (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 microorganisms. However, IL-12 also appears to play a central role in the pathogenesis of autoimmune diseases such as multiple sclerosis or rheumatic arthritis. Therefore, it is crucial to understand how IL-12 is produced and its production is regulated at the molecular level. IL-12 production is differentially regulated through multiple pathways, which can be classified as follows: nuclear factor-kappaB (NF-kappaB) and other transcription factors, p38 mitogen-activated protein (MAP) kinase, cyclic adenosine monophosphate (cyclic AMP)-modulating molecules, cell membrane ion channels and pumps, nitric oxide (NO), and receptors. In this review we describe the regulatory mechanisms of IL-12 production in immune cells and also some agents to control IL-12 production for the treatment of immune-related diseases.