Increased circulating levels of interleukin 33 in systemic sclerosis correlate with early disease stage and microvascular involvement.

摘要

Early activation/damage of endothelial cells and multiple profibrotic T helper type 2 (Th2)-associated cytokines play an important role in the pathogenesis of systemic sclerosis (SSc). Interleukin 33 (IL-33) was recently identified as a member of the IL-1 family and a ligand for the orphan receptor ST2L, which mediates the action of IL-33 on polarised Th2 lymphocytes and other leucocyte subsets, and tissue-resident cells, such as vascular endothelial cells and fibroblasts/myofi-broblasts. IL-33 has been shown to induce IL-13-dependent cutaneous fibrosis and stimulate angiogenesis and vascular permeability. In healthy human tissues IL-33 protein is con-stitutively highly expressed in the nuclei of resting endothelial cells, but rapidly lost upon angiogenic or proinflammatory activation. Indeed, IL-33 is thought to function as an endogenous 'alarmin' that is rapidly released after endothelial cell damage to alert the cells of the innate and adaptive immune system.