Interleukin-12 (IL-12), also known as natural killer cell stimulatory factor (NKSF) or cytotoxic lymphocyte maturation factor (CLMF), is a pleiotropic cytokine originally identified in the medium of activated human B lymphoblastoid cell lines (1). The p40 subunit of IL-12 has been shown to have extensive amino acid sequence homology to the extracellular domain of the human IL-6 receptor while the p35 subunit shows distant but significant sequence similarity to IL-6, G-CSF, and chicken MGF (2, 3). These observations have led to the suggestion that IL-12 might have evolved from a cytokine/soluble receptor complex. Human and murine IL-12 share 70% and 60% amino acid sequence homology in their p40 and p35 subunits, respectively. IL-12 apparently shows species specificity with human IL-12 reportedly showing minimal activity in the murine system. IL-12 is produced by macrophages and B lymphocytes and has been shown to have multiple effects on T cells and natural killer (NK) cells (4). These effects include inducing production of IFN-r and TNF by resting and activated T and NK cells, synergizing with other IFN-gamma inducers at both the transcriptional and post-transcriptional levels. This interaction induces IFN-gamma gene expression, enhancing the cytotoxic activity of resting NK and T cells, inducing and synergizing with IL-2 in the generation of lymphokine-activated killer (LAK) cells, acting as a co-mitogen to stimulate proliferation of resting T cells, and inducing proliferation of activated T and NK cells (5). Current evidence indicates that IL-12, produced by macrophages in response to infectious agents, is a central mediator of the cell-mediated immune response by its actions on the development, proliferation, and activities of TH1 cells. In its role as the initiator of cell-mediated immunity, it has been suggested that IL-12 has therapeutic potential as a stimulator of cell-mediated immune responses to microbial pathogens, metastatic cancers, and viral infections such as AIDS.

1. Gubler, U. et al. (1991) Proc. Natl. Acad. Sci. 88:4143.

2. Gearing, D. et al. (1991) Cell 66:9.

3. Merberg, D. et al. (1992) Immunology Today 13:78.

4. Wolf, S.F. et al. (1991) Journal of Immunology 146:3074.

5. Airoldi, I. et al. (2000) Journal of Immunology 165:6880.