TNF-ALPHA, UNLIKE OTHER PRO-INFLAMMATORY AND ANTIINFLAMMATORY CYTOKINES, INDUCES RAPID RELEASE OF THE IL-1 TYPE-II DECOY RECEPTOR IN HUMAN MYELOMONOCYTIC CELLS

The present study was designed to investigate the effect of a series o f cytokines on the release of the type II IL-1 decoy receptor, which r epresents a unique pathway of negative regulation of the IL-1 system. After 20 min, IL-1, IL-2, IL-4, IL-6, IL-10, IL-12, IL-13, IFN-gamma, granulocyte-CSF, macrophage-CSF, and TGF-beta had little or no effect on IL-1 binding by human polymorphonuclear cells. In contrast granuloc yte-macrophage-CSF and, to a greater extent, TNF markedly reduced IL-1 binding. The action of TNF was rapid, reaching 50% of its maximum (80 %) at 2 min, and plateauing at 20 min with decrease in receptor number and no significant change in affinity. Loss of surface receptor was a ssociated to rapid release of a 45-kDa IL-1-binding molecule identifie d as the decoy RII. TNF-induced release of the decoy RII was independe nt of protein synthesis and reactive oxygen intermediates. Monocytes s howed a similar response to TNF, except for the size of the released m olecule (approximate to 60 kDa). TNF induced rapid release of its own receptors. In contrast IL-1 beta affected neither its own receptors no r the TNF-R. TNF and, more efficiently, PMA caused release of the deco y RII in fibroblasts transfected with the full-length decoy RII or wit h a cytoplasmatic deletion mutant. TNF-induced decoy RII release repre sents an unidirectional pathway of communication in the interplay betw een the IL-1 and TNF system.