Crystal-induced activation of the inflammasome: gout and pseudogout

Crystals in tissues lead the innate immune system to the same kind of acute response seen with pathogens. Via activation of the inflammasome, interleukin-1 (IL-1) is released, which upregulates mediators such as cyclooxygenase, tumor necrosis factor, and IL-8 and induces an acute granulocytic inflammation. Therefore, in addition to nonsteroidal anti-inflammatory drugs (NSAIDs), steroids, and colchicine, IL-1 blockers appear to be effective. Large clinical trials have already been initiated. Such an approach could constitute a valuable alternative for patients with contraindications or insufficient response to NSAIDs. After the attack has subsided, control of uric acid metabolism is central. At least several of the responsible urate transporters have been unraveled, which could lead to more focused therapy in the future. At present, diet and blockade of uric acid synthesis remain the main pillars of therapy. The new xanthine oxidase inhibitor febuxostat constitutes a novel option for patients with renal insufficiency or intolerance to allopurinol.