[Biological properties and clinical significance of interleukins 12 (IL-12)]

IL-12 is a heterodimeric cytokine composed of 2 disulfide-linked subunits with molecular masses of 40 and 35 kDa, respectively. The cytokine is produced by phagocytic cells, professional antigen-presenting cells such as dendritic cells, skin Langerhans cells and B cells. IL-12 production is induced by bacteria, intracellular pathogens, fungi, viruses, or their products in a T-cell-independent pathway or a T-cell-dependent pathway, the latter mediated through CD40 ligand-CD40 interaction. Interleukin 12 induces interferon gamma secretion by T cells and natural killer cells, enhances the proliferation of activated T cells and natural killer cells, augments the cytolytic activity of cytotoxic T lymphocytes and natural killer cells, and supports the differentiation of Th1 helper effector cells. The therapeutic potential of these activities is suggested by studies in tumor and microbial models. IL-12 has suppressed tumor growth in all murine models examined. Antimicrobial activity has been demonstrated in bacterial, parasitic, and viral models of infection. The cytokine also stimulates in vitro antitumor activity of lymphocytes from patients with cancer. Current data indicate that CD4 T cells, CD8 T cells, natural killer cells and interferon-gamma may contribute to the antitumor effects of interleukin-12 therapy. Clinical trials are being initiated to evaluate the possible therapeutic uses of IL-12 in the treatment of neoplastic diseases and some infections.