“The biological activity of the cytokine Interleukin-12 makes it a very important molecule that regulates the body resistance to infections and cancer.”

The paper is a comprehensive review of the role of the cytokine Interleukin-12 (IL-12) and of other recently described members of the family of heterodimeric cytokines in innate resistance and adaptive immunity. IL-12 was the first heterodimeric cytokine to be described, and it has been shown to play a key role in regulating both innate and adaptive immunity. IL-12 is produced early on during infections or inflammatory responses by phagocytic cells and dendritic cells, the most potent antigen-presenting cells. IL-12, acting together with other pro-inflammatory cytokines and cell-to-cell signals, induce natural killer (NK) cells and certain T lymphocytes to rapidly produce Interferon-γ (IFN-γ). IFN-γ is one of the most powerful cytokines activating the functions of phagocytic cells such as macrophages and neutrophils, thus contributing to the amplification of the inflammatory and natural resistance response. Most importantly, IL-12, directly and through its ability to induce early IFN-γ production, also determines the differentiation and potency of the T helper type 1 immune response (Th-1) that is required for optimal resistance against many infectious pathogens and cancers, and that is also the class of immune response responsible for the pathogenesis of many organ-specific autoimmune disorders. Thus, IL-12 is an important bridge between natural resistance and adaptive immunity. Recently, a few other heterodimeric cytokines have been identified (e.g.,IL-23 and IL-27) that may share or complement some of the proinflammatory and immunomodulating activities of IL-12. In particular IL-23 has one chain—the p40 heavy chain or β chain—in common with IL-12. Antibodies against this common chain, or mice genetically deficient for it, have often been used for the studies of the physiologic function of IL-12; but this approach did not allow the investigators to distinguish between the functions of IL-12 and IL-23. Indeed, recent studies published by a group of investigators at DNAX (Palo Alto, CA) have now indicated that some of the functions attributed to IL-12 in autoimmunity may indeed be mediated by IL-23 or by a combined effect of IL-12 and IL-23. The reciprocal role of IL-12, IL-23, and IL-27 in the immune response is now a very active field of investigation, justifying the high interest and citation for this review.