INTERLEUKIN-12 - A KEY MODULATOR OF IMMUNE FUNCTION

Interleukin (IL)-12 was cloned on the basis of its ability to activate natural killer (NK) cells and promote the development of cytolytic T cells. With further understanding of its activities, IL-12 has emerged as an important cytokine, affecting both immune and hematologic funct ions. It has been shown to be necessary for the T cell independent ind uction of interferon (IFN)-gamma, critical for the initial suppression of bacterial and parasitic infection: for the development of a Th1 re sponse, critical for effective host defense against intracellular path ogens; and for the activation of differentiated T lymphocytes of both CD4+ and CD8+ phenotype, IL-12 thus functions to activate and to link the innate and acquired immune responses. The therapeutic potential of these activities is suggested by studies in tumor and microbial model s. IL-12 has suppressed tumor growth in all murine models examined. An timicrobial activity has been demonstrated in bacterial, yeast, parasi tic, and viral models of infection. In many of these models, activity has been linked to production of IFN-gamma and, in the parasite model, to development of a Th1 response. In addition to the therapeutic pote ntial associated with IL-12 activity in these disease models, the unde rstanding of its role in immune development and interaction with other cytokines, particularly antagonists, such as IL-4 and IL-10, has clar ified and extended our understanding of immune regulation and should l ead to significant developments in understanding the progression of AI DS and the development of vaccine adjuvants able to direct the immune response.