Background
IL-1α is synthesized as a precursor (preIL-1α), which is processed into mature IL-1α and a N-terminal propeptide by calpain-like proteases. Besides its classical effects elicited upon IL-1 receptor binding, preIL-1α exerts intracellular functions, including the modulation of cell growth and apoptosis. Nuclear translocation of preIL-1α, mediated by the N-terminal propeptide, is required for these effects. IL-1 receptor antagonist (IL-1Ra) inhibits the classical effects of IL-1 by preventing the interaction of IL-1 with its receptor. Four different isoforms of IL-1Ra have been described, of which one is secreted and three others are intracellular (icIL-1Ra1, icIL-1Ra 2, icIL-1Ra 3). Due to their intracellular localization, icIL-1Ras cannot interact with cell surface receptors and have been suggested to carry out specific functions inside cells. The description of nuclear functions for preIL-1α suggested that icIL1Ra variants might antagonize intracellular effects of preIL-1α.