The soluble form of IL-1 receptor accessory protein enhances the ability of soluble type II IL-1 receptor to inhibit IL-1 action

Regulation of the activity of the proinflammatory cytokine IL-1 is complex, involving transcriptional and translational control, precursor processing, a receptor antagonist (IL-1RA), and a decoy receptor. Here we report that the soluble form of the IL-1 receptor accessory protein (AcP) increases the affinity of binding of human IL-1alpha and IL-1beta to the soluble human type II IL-1 receptor by approximately 100-fold, while leaving unaltered the low binding affinity of IL-1RA. Soluble AcP is present in normal human serum at an average concentration greater than 300 ng/ml. These findings suggest that the soluble form of IL-1R AcP contributes to the antagonism of IL-1 action by the type II decoy receptor, adding another layer of complexity to the regulation of IL-1 action.