Interleukin (IL)-4 is a major regulatory cytokine governing bioactive IL-12 production by mouse and human dendritic cells

Interleukin (IL)-12 may be secreted as a bioactive T helper type 1 (Th1) ce ll-inducing heterodimer, as a monomer, or as an antagonistic homodimer. We analyzed the IL-12 produced by mouse splenic dendritic cells (DCs), human t hymic DCs, and cultured human monocyte-derived DCs. IL-12 production requir ed both a microbial or T cell-derived stimulus and an appropriate cytokine milieu. The different IL-12 forms were differentially regulated by the cyto kines present rather than the stimulus used. IL-4 alone or together with gr anulocyte/macrophage colony-stimulating factor or interferon gamma effectiv ely enhanced the production of the bioactive heterodimer and selectively re duced the antagonistic homodimer of IL-12. Therefore, IL-4, the major Th2-d riving cytokine, provides a negative feedback causing DCs to produce the ma jor Th1-inducing cytokine, bioactive IL-12.