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Mice with the beige mutation are known to be deficient for polymorphonuclear leucocyte (PMN) elastase and cathepsin G and can therefore be used as a model for protease dependence of tissue destruction in inflammatory conditions. The in vitro and in vivo effect of PMN activation on cartilage damage in C57black/6 normal and beige mice was measured. In vitro it was found that stimulation of normal PMNs with chemotactic peptide caused degradation of articular cartilage matrix owing to an elastase dependent mechanism; PMNs of beige mice did not induce degradation of cartilage. In vivo, using zymosan induced arthritis, which is a model characterised by a PMN-rich infiltrate and exudate, no significant differences were found between the two strains with respect to (a) joint oedema formation as measured by technetium-99m uptake; (b) matrix degradation as measured quantitatively and with histology; (c) chondrocyte proteoglycan synthesis as measured by radiosulphate uptake. At day 28 after induction of arthritis, when inflammation is waning, no differences in end stage irreversible damage to joint tissues were found. The relevance of these observations to the supposed role of PMN derived neutral proteases in joint inflammation is discussed. [ABSTRACT FROM PUBLISHER]

Objectives: Schnitzler's syndrome is a chronic disabling autoinflammatory disorder, characterised by chronic urticaria, paraproteinemia and systemic inflammation. The interleukin (IL) 1 receptor antagonist anakinra is a very effective treatment, but requires daily injection and blocks both IL-1α and IL-1β. Canakinumab is a selective human monoclonal anti-IL-1β antibody with a long half-life. We investigated the long-term efficacy and safety of canakinumab in Schnitzler's syndrome., Methods: In an open-label, single-treatment arm trial, eight patients with Schnitzler's syndrome received monthly injections with 150 mg canakinumab subcutaneously for 6 months, followed by a 3-month observation period. Primary outcome was complete or clinical remission at day 14. Secondary outcome measures included inflammatory markers, quality of life, time to relapse, safety and tolerability., Results: After stopping anakinra, patients developed moderate to severe clinical symptoms. Canakinumab induced complete or clinical remission at day 14 in all eight patients. Median C-reactive protein concentrations decreased from 169 mg/l at baseline to less than 10 mg/l on day 14 and remained low or undetectable. One patient discontinued participation on day 39 because of return of symptoms while all others remained in complete or clinical remission during the 6-month treatment period. Relapse after last canakinumab dose occurred within 3 months in four patients. For two patients, remission continued several months post-study. Five patients reported at least one adverse event, predominantly mild upper respiratory tract infections. One patient died in a traffic accident., Conclusions: In this 9-month study, monthly 150 mg canakinumab injection was an effective and well-tolerated treatment for Schnitzler's syndrome. Our data demonstrate that IL-1β plays a pivotal role in this disease. CLINICALTRIALS.GOV: NCT01276522.