The interleukin-12 family of cytokines: Therapeutic targets for inflammatory disease mediation

Abstract

The interleukin (IL)-12 family of cytokines, including IL-12 and IL-23, are important mediators of immune-mediated inflammatory diseases such as psoriasis, multiple sclerosis, rheumatoid arthritis, and Crohn's disease. Interleukin-12 and IL-23 are heterodimeric proteins composed of the common subunit IL-12 p40, which interacts with the IL-12Rβ1 receptor, and the cytokine-specific subunits IL-12 p35 and IL-23 p19, respectively. The cytokines are proinflammatory factors linking innate and adaptive immune responses via the induction and differentiation of the T helper cell 1 pathway. Interleukin-12 and IL-23 target different subpopulations of T cells and antigen-presenting cells, as evidenced by their slightly different, but possibly clinically significant, characteristics and functions. Because both share the p40 subunit, the use of anti-IL-12 antibodies may not be as clinically effective as the use of anti-IL-12 p40 antibodies, since both IL-12 and IL-23 share the subunit, which compete, for the IL-12Rβ1 receptor. Also, while IL-12 is a key factor that drives T helper cell 1 responses and interferon-gamma production in the early phases of the immune responses, it may play a relatively minor immunoregulatory role in late-stage inflammation at the point when IL-23 strongly supports the inflammatory process. Thus, direct IL-23 blockade may be key in treating some inflammatory autoimmune diseases as we further define the roles and functions of IL-12 and IL-23. Research into the function and regulation of IL-12 and IL-23 is a promising area of study for inflammatory disease mediation, and inhibition of their actions may have clinical therapeutic applications.