Interleukin-13 (IL-13) induces IL-1 receptor antagonist gene expression and protein synthesis in peripheral blood mononuclear cells: inhibition by an IL-4 mutant protein

Interleukin-13 (IL-13) belongs to the IL-4 gene family. Like IL-4, IL- 13 induces IL-1 receptor antagonist (IL-1Ra) synthesis with no effect on IL-1beta synthesis. We investigated whether IL-13 induces IL-1Ra synthesis via a pathway similar to IL-4. In human peripheral blood mononuclear cells, IL-13 (1 to 100 ng/mL alone induced IL-1Ra synthesis in a dose-dependent manner. A single amino acid mutant form of IL-4 (hIL4.Yl24D) induced IL-1Ra synthesis, acting as a partial agonist. However, hIL-4.Yl24D inhibited IL-1Ra synthesis induced by either IL-4 or IL-13. IL-13 alone induced accumulation of IL-1Ra mRNA. Furthermore, IL-13 reduced steady- state levels for IL-1beta mRNA but enhanced those for IL-1Ra mRNA in cells stimulated with lipopolysaccharide (LPS) or IL- 1alpha. Accordingly, IL-13 suppressed IL-1beta synthesis but enhanced IL-1Ra synthesis in these cells. IL-13 reduced the stability of IL- 1beta mRNA (2.9 v 1.7 hours) but failed to modify the stability of IL- 1Ra mRNA (2.7 v 2.5 hours). Moreover, IL-13 induced transcriptional activation of the IL-1Ra gene, but reduced IL-1beta gene transcription. Our results suggest that the commonality between IL-13 and IL-4 in inducing IL-1Ra synthesis results from the engagement of a subunit common to both receptors.