Rapid Publication Recombinant Interleukin-12 Suppresses the Synthesis

Interleukin-12 is a recently discovered lymphokine displaying an array of in vitro activities suggesting a major role in protec-tive immunity against infectious agents like viruses. This study provides evidence that IL-12 may also be implicated in the selection of the immunoglobulin isotypes. We show that pico-molar concentrations of rIL-12 markedly inhibit the synthesis of IgE by IL4-stimulated PBMC. The suppression of IgE is observed at the protein and at the mRNA levels, it is isotype specific, and it is abolished by neutralizing anti-IL-12 mAbs. IL-12 may suppress IgE synthesis by: (a) inducing the produc-tion of IFN-y, a known inhibitor of IgE synthesis and (b) by a novel mechanism which is IFN-y independent. The best evi-dence for this is from studies on IgE synthesis by IL-4-plus hydrocortisone-stimulated umbilical cord blood lymphocytes, which do not produce detectable amounts of IFN-'y. In such cultures, rIL-12 inhibits IgE synthesis even in the presence ofa large excess of neutralizing anti-IFN-y mAb. (J. Clin. Invest