Induction of immunity and inflammation by interleukin-12 family members

The interleukin (IL)-12 family is composed of three heterodimeric cytokines, IL-12 (p40p35), IL-23 (p40p19), and IL-27 (EBt3p28), and of monomeric and homodimeric p40. This review focuses on the three heterodimeric members of the IL-12 family, The p40 and p40-like (EB13) subunits have homology to the IL-6R, the other subunits (p35, p 19, and p28) are homologous to each other and to members of the IL-6 superfamily. On the basis of their structural similarity, it was expected that the members of the IL-12 family have overlapping pro-inflammatory and immunoregulatory functions. However, it was surprising that they also show very distinct activities. IL-12 has a central role as a Th1-inducing and -maintaining cytokine, which is essential in cell-mediated immunity in nonviral infections and in tumor control. IL-23 recently emerged as an end-stage effector cytokine responsible for autoimmune chronic inflammation through induction of IL-17 and direct activation of macrophages. Very recently, IL-27 was found to exert not only a pro-inflammatory Th1-enhancing but also a significant anti-inflammatory function.