Cloning and sequencing of horse interleukin-12 and interleukin-18 cDNAs

Interleukin-12 (IL-12) and interleukin-18 (IL-18) are key cytokines in the modulation of cell-mediated immune responses. IL-12 is produced primarily by macro-phages and dendritic cells in response to intracellular parasites, bacteria, and their products. First identified by its synergy with IL-2 in the stimulation of the activity of T cells and natural killer (NK) cells, it is now known that this molecule plays a central role in the modulation of immune responses. The effects of IL-12 include the enhancement of lytic activity and IFN- gamma secretion by NK and T cells, the inhibition of IL-2-driven proliferation of NK cells, the potent proliferation induction of both naive and memory T cells, and the induction of T-helper type 1 (TH1) differentiation. Biologically active human IL-12 is a 70 000 M sub(r) heterodimer comprising covalently linked glycosylated peptides of approximately 40 000 and 35 0000 M sub(r), designated p40 and p35 respectively. Sequence similarity of p35 to IL-6 and granulocyte colony stimulating factor (G-CSF) and of p40 to the IL-6 and G-CSF receptors are suggestive of evolution from a common primordial cytokine and a p70 structure akin to a soluble cytokine:cytokine receptor complex.