Interleukin-11 inhibits macrophage interleukin-12 production.
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.
Leng
S X
SX
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
Elias
J A
JA
D003864:Depression, Chemical; D004306:Dose-Response Relationship, Immunologic; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D017370:Interleukin-11 / Q000494:pharmacology*; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D007378:Interleukins / Q000494:pharmacology; D007948:Leukemia, Monocytic, Acute / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D017370:Interleukin-11; D007378:Interleukins; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D018664:Interleukin-12; D007371:Interferon-gamma