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  • Title: Recombinant interleukin-12 suppresses the synthesis of immunoglobulin E by interleukin-4 stimulated human lymphocytes.
    Author: Kiniwa M, Gately M, Gubler U, Chizzonite R, Fargeas C, Delespesse G.
    Journal: J Clin Invest; 1992 Jul; 90(1):262-6. PubMed ID: 1353081.
    Abstract:
    Interleukin-12 is a recently discovered lymphokine displaying an array of in vitro activities suggesting a major role in protective 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 picomolar concentrations of rIL-12 markedly inhibit the synthesis of IgE by IL-4-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 production of IFN-gamma, a known inhibitor of IgE synthesis and (b) by a novel mechanism which is IFN-gamma independent. The best evidence 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-gamma. In such cultures, rIL-12 inhibits IgE synthesis even in the presence of a large excess of neutralizing anti-IFN-gamma mAb.
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