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-1 beta synthesis. We investigated whether IL-13 induces IL-1Ra s ynthesis via a pathway similar to IL-4. In human peripheral blood mono nuclear cells, IL-13 (1 to 100 ng/mL) alone induced IL-1Ra synthesis i n a dose-dependent manner. A single amino acid mutant form of IL-4 (hl L-4.Y124D) induced IL-1Ra synthesis, acting as a partial agonist. Howe ver, hlL-4.Y124D inhibited IL-1Ra synthesis induced by either IL-4 or IL-13. IL-13 alone induced accumulation of IL-1Ra mRNA. Furthermore, I L-13 reduced steady-state levels for IL-1 beta mRNA but enhanced those for IL-1Ra mRNA in cells stimulated with lipopolysaccharide (LPS) or lL-1 alpha. Accordingly, IL-13 suppressed IL-1 beta synthesis but enha nced IL-1Ra synthesis in these cells. IL-13 reduced the stability of I L-1 beta 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-1 beta gene transcripti on. Our results suggest that the commonality between IL-13 and IL-4 in inducing IL-1Ra synthesis results from the engagement of a subunit co mmon to both receptors. (C) 1996 by The American Society of Hematology .