Recombinant lnterleukin-12 suppresses the synthesis of immunoglobulin E by lnterleukin-4 stimulated human lymphocytes

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Abstract

InterIeukin-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-γ, a known inhibitor of IgE synthesis and (b) by a novel mechanism which is IFN-γ 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-γ. In such cultures, rIL-12 inhibits IgE synthesis even in the presence of a large excess of neutralizing anti-IFN-γ mAb.

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Kiniwa, M., Gately, M., Gubler, U., Chizzonite, R., Fargeas, C., & Delespesse, G. (1992). Recombinant lnterleukin-12 suppresses the synthesis of immunoglobulin E by lnterleukin-4 stimulated human lymphocytes. Journal of Clinical Investigation, 90(1), 262–266. https://doi.org/10.1172/jci115846

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