Interleukin-11 inhibits macrophage interleukin-12 production.

SX Leng, JA Elias - Journal of immunology (Baltimore, Md.: 1950), 1997 - journals.aai.org
SX Leng, JA Elias
Journal of immunology (Baltimore, Md.: 1950), 1997journals.aai.org
IL-12 is a heterodimeric cytokine produced by phagocytic and other cells with important
physiologic and pathologic properties. Regulated IL-12 production is crucial for the
generation of protective Th1 responses to infectious agents. In contrast, IL-12 excess
contributes to the pathogenesis of a variety of autoimmune and inflammatory disorders. To
further understand the processes regulating IL-12 production, we determined whether IL-11
regulated monocyte/macrophage production of this cytokine moiety. IL-11 did not alter the IL …
Abstract
IL-12 is a heterodimeric cytokine produced by phagocytic and other cells with important physiologic and pathologic properties. Regulated IL-12 production is crucial for the generation of protective Th1 responses to infectious agents. In contrast, IL-12 excess contributes to the pathogenesis of a variety of autoimmune and inflammatory disorders. To further understand the processes regulating IL-12 production, we determined whether IL-11 regulated monocyte/macrophage production of this cytokine moiety. IL-11 did not alter the IL-12 (p70) production of unstimulated THP-1 monocytic cells or human blood monocytes. It did, however, inhibit, in a dose-dependent fashion, the IL-12 production of IFN-gamma plus Staphylococcus aureus Cowan strain 1-stimulated THP-1 cells and stimulated blood monocytes. This inhibition of IL-12 protein production was associated with a proportionate decrease in IL-12 p35 and p40 mRNA accumulation. Nuclear run-on assays revealed comparable decreases in IL-12 p35 and p40 gene transcription. IL-11 did not similarly regulate monocyte/macrophage production of IL-8 or macrophage inflammatory protein-1alpha (MIP-1alpha) and IL-6 did not similarly inhibit IL-12 elaboration. These studies demonstrate that IL-11 is a potent inhibitor of monocyte/macrophage IL-12 production and that this inhibitory effect is, at least in part, transcriptionally mediated. They also demonstrate that this inhibition is not the result of a generalized suppression of macrophage effector function and that the ability to inhibit monocyte/macrophage IL-12 production is not a generalized property of all IL-6-type cytokines.
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