IL-12

Abstract

Interleukin-12 (IL-12) is a heterodimeric cytokine produced mostly by phagocytic cells in response to bacteria, bacterial products, and intracellular parasites. IL-12 induces cytokine production, primarily of IFN-γ, from NK and T cells, acts as a growth factor for activated NK and T cells, enhances the cytotoxic activity of NK, LAK cells, and favors cytotoxic T lymphocyte generation. IL-12 acts primarily at three distinct stages during the innate to adaptive immune response to infection: First it is produced and induces production from NK and T cells of IFN-γ, which contributes to phagocytic cell activation and inflammation; second, IL-12 and IL-12-induced IFN-γ favor Th1 cell differentiation by priming CD4+ T cells for high IFN-γ production ; third, IL-12 contributes to optimal IFN-γ production and to proliferation of differentiated Th1 cells in response to antigen. Thus, IL-12 represents a functional bridge between the early innate immunity and the subsequent antigen-specific adaptive immunity. Its activities are mediated through a high-affinity receptor composed of two subunits, designated β1, and β2. Of these two subunits, β2 expression is likely the central mechanism by which IL-12 responsiveness is controlled. Endogenous IL-12 plays a pivotal role in the normal host defense against infection by a variety of intracellular pathogens. Inhibition of IL-12 synthesis or activity may be beneficial in disease associated with pathologic Th1 responses, such as multiple sclerosis, rheumatoid arthritis, hepatitis, or Crohn's disease. On the other hand, administration of recombinant IL-12 may be useful in the treatment of diseases associated with pathologic Th2 responses such as allergic disorders, atopic dermatitis and asthma.