Recombinant Fc-IL-18BPc isoform inhibits IL-18-induced cytokine production

IL-18 is a pro-inflammatory cytokine that is produced from T cells and NK cells. IL-18 has been implicated in the pathogenesis of various inflammatory and cardiovascular diseases. IL-18 binding protein (IL-18BP) is a natural inhibitor of IL-18 that possesses higher affinity to IL-18 than that of the IL-18 receptor alpha chain on the cell surface. Human isoform a and c among four isoforms of IL-18BPs have an inhibitory effect on IL-18-induced cytokines whereas mouse IL-18BP isoforms exist only in two isoforms: c and d. Fc-fusion protein is a molecule in which the immunoglobulin Fc is fused genetically to a protein of interest, such as an extracellular domain of a receptor, ligand, or enzyme. In this study, we expressed and purified human Fc-IL-18BPa and c isoforms from CHO-DG44 cells and their biological activities were compared to each other. This is the first time that expressed recombinant human Fc-IL-18BPc has been examined for its biological activity on IL-18-induced IFNγ in human PBMC and IL-6 in A549/IL-18Rβ.