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Background
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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 cultured EBV-transformed RPMI-8866 cells . IL-12 is a 75 kDa glycoprotein heterodimer composed of two genetically unrelated subunits linked by a disulfide bond. The smaller subunit (p35) has homology to IL-6 and G-CSF while the larger subunit (p40) demonstrates similarity to the soluble receptor for IL-6, leading to the suggestion that IL-12 might have evolved from a cytokine/soluble receptor complex . Each subunit of IL-12 apparently arises from a single copy gene. The mRNA transcription of the subunits is closely coordinated, although an excess of the larger subunit has been shown to be produced by B cells in addition to active IL-12 . Expression of p35 is reported to be enhanced by simultaneous expression of p40. IL-12 activity cannot be demonstrated in the absence of either chain . As suggested by their names, p35 has a native molecular weight of 35 kDa while p40 has a native molecular weight of 40 kDa. 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 . These include inducing production of IFN-gama and TNF by resting and activated T and NK cells, synergizing with other IFN-gama inducers at both the transcriptional and post-transcriptional levels to induce IFN- gama 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 comitogen to stimulate proliferation of resting T cells, and inducing proliferation of activated T and NK cells . 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 . These activities of IL-12 are antagonized by IL-4 and IL-10, factors associated with the development of uncommitted T helper cells into TH2 cells and mediation of the humoral immune response .
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