Interleukin-12: an Immunoregulatory Cytokine Produced by B Cells and Antigen-presenting Cells

Interleukin 12 (IL-12) is a heterodimeric protein produced by B cells, phagocytic cells, and other antigen-presenting cells. IL-12 was originally purified from the supernatant fluids of human EBV-transformed cell lines and later observed to be produced by the large majority of such cell lines, especially and at high levels from those derived from AIDS-associated lymphomas. However, phagocytic cells rather than B cells appear to be the most important physiological producers of IL-12. There are two pathways of IL-12 induction in phagocytic cells: a T-cell-independent one, induced primarily by bacteria, bacterial products, or intracellular parasites and important in the early inflammatory response of innate resistance; and a T-cell-dependent one, induced by the interaction of CD40L on activated T cells with CD40 receptor on IL-12-producing cells (phagocytic cells and antigen-presenting cells) and important in the regulation of adaptive immunity. IL-12 induces production of cytokines, especially interferon-gamma, from both T and NK cells, enhances the cytotoxic activity of NK cells and the generation of cytotoxic T cells, and has a proliferative activity on T and NK cells. Both in vivo and in vitro, IL-12 is a powerful inducer of T helper type 1 (Th1) response, whereas it inhibits Th2-type responses.