Activation of the inflammasome, a protein complex responsible for many cellular functions,
including the activation of the proinflammatory cytokines interleukin (IL)-1β and
IL-18, has been identified as a key participant in many rheumatic diseases including
autoimmune, inflammatory, and autoinflammatory syndromes. This review will discuss
the recent advances in understanding the role of this complex in various rheumatic
diseases. Furthermore, it will focus on available therapies, which directly and indirectly
target the inflammasome and its downstream cytokines to quiet inflammation and possibly
dampen autoimmune processes.
Abbreviations:
AIM2 (Absent in Melanoma 2), AOSD (adult-onset Still's disease), AS (ankylosing spondylitis), ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain), CAPS (cryopyrin-associated periodic syndrome), CARD (caspase-recruitment domain), CPPD (calcium pyrophosphate dehydrate), FA (fatty acids), FMF (familial Mediterranean fever), HIDS (hyperimmunoglobulinemia D syndrome), IL (interleukin), IL-1RA (IL-1 receptor antagonist), MSU (monosodium urate), NFκB (nuclear factor κB), NLR (nod-like receptor), NOMID (neonatal-onset multisystem inflammatory disease), NSAID (nonsteroidal anti-inflammatory drug), PAPA (pyogenic sterile arthritis, pyoderma gangrenosum and acne), PBMCs (peripheral blood mononuclear cells), RA (rheumatoid arthritis), RIG-I (retinoic acid–inducible gene I), ROS (reactive oxygen species), s-JIA (systemic onset juvenile idiopathic arthritis), SLE (systemic lupus erythematosus), TLR (toll-like receptor), TRAPS (tumor necrosis factor receptor–associated periodic syndrome)To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Translational ResearchAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Inflammasomes and their roles in health and disease.Annu Rev Cell Dev Biol. 2012; 28: 137-161
- Caspase-1-induced pyroptosis is an innate immune effector mechanism against intracellular bacteria.Nat Immunol. 2010; 11: 1136-1142
- Activation and regulation of the inflammasomes.Nat Rev Immunol. 2013; 13: 397-411
- Recognition of RNA virus by RIG-I results in activation of CARD9 and inflammasome signaling for interleukin 1 beta production.Nat Immunol. 2010; 11: 63-69
- Cutting edge: NF-κB activating pattern recognition and cytokine receptors license NLRP3 inflammasome activation by regulating NLRP3 expression.J Immunol. 2009; 183: 787-791
- Potentiation of caspase-1 activation by the P2X7 receptor is dependent on TLR signals and requires NF-kappaB-driven protein synthesis.J Immunol. 2005; 175: 7611-7622
- Non-transcriptional priming and deubiquitination regulate NLRP3 inflammasome activation.J Biol Chem. 2012; 287: 36617-36622
- Non-transcriptional regulation of NLRP3 inflammasome signaling by IL-4.Immunol Cell Biol. 2015; ([Epub ahead of print])
- Regulation of inflammasome activation.Immunol Rev. 2015; 265: 6-21
- Differential requirement of P2X7 receptor and intracellular K+ for caspase-1 activation induced by intracellular and extracellular bacteria.J Biol Chem. 2007; 282: 18810-18818
- Inflammasomes as microbial sensors.Eur J Immunol. 2010; 40: 611-615
- Uric acid as a danger signal in gout and its comorbidities.Nat Rev. 2013; 9: 13-23
- Self double-stranded (ds) DNA induces IL-1β production from human monocytes by activating NLRP3 inflammasome in the presence of anti–dsDNA antibodies.J Immunol. 2013; 190: 1407-1415
- Memory regulatory T cells reside in human skin.J Clin Invest. 2014; 124: 1027-1036
- Treating inflammation by blocking interleukin-1 in a broad spectrum of diseases.Nat Rev Drug Discov. 2012; 11: 633-652
- Pralnacasan, an inhibitor of interleukin-1beta converting enzyme, reduces joint damage in two murine models of osteoarthritis.Osteoarthritis Cartilage. 2003; 11: 738-746
- A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases.Nat Med. 2015; 21: 248-255
- The cytokine release inhibitory drug CRID3 targets ASC oligomerisation in the NLRP3 and AIM2 inflammasomes.PLoS One. 2011; 6: e29539
- Glyburide inhibits the CRYOPYRIN/Nalp3 inflammasome.J Cell Biol. 2009; 187: 61-70
- Omega-3 fatty acids prevent inflammation and metabolic disorder through inhibition of NLRP3 inflammasome activation.Immunity. 2013; 38: 1154-1163
- Thalidomide inhibits activation of caspase-1.J Immunol. 2009; 183: 5593-5599
- Thalidomide: still an important second-line treatment in refractory cutaneous lupus erythematosus?.J Dermatolog Treat. 2015; 26: 173-177
- U1-small nuclear ribonucleoprotein activates the NLRP3 inflammasome in human monocytes.J Immunol. 2012; 188: 4769-4775
- Preliminary results of safety and efficacy of the interleukin 1 receptor antagonist anakinra in patients with severe lupus arthritis.Ann Rheum Dis. 2005; 64: 630-633
- Microtubule-driven spatial arrangement of mitochondria promotes activation of the NLRP3 inflammasome.Nat Immunol. 2013; 14: 454-460
- Cyclooxygenase-2 regulates NLRP3 inflammasome-derived IL-1beta production.J Cell Physiol. 2015; 230: 863-874
- Interferon-alpha in systemic lupus erythematosus.Curr Opin Rheumatol. 2004; 16: 541-547
- Age-specific incidence rates of myocardial infarction and angina in women with systemic lupus erythematosus: comparison with the Framingham Study.Am J Epidemiol. 1997; 145: 408-415
- Inflammasome activation of IL-18 results in endothelial progenitor cell dysfunction in systemic lupus erythematosus.J Immunol. 2011; 187: 6143-6156
- Expression profile of HIN200 in leukocytes and renal biopsy of SLE patients by real-time RT-PCR.Lupus. 2009; 18: 1066-1072
- C3a modulates IL-1β secretion in human monocytes by regulating ATP efflux and subsequent NLRP3 inflammasome activation.Blood. 2013; 122: 3473-3481
- Netting neutrophils induce endothelial damage, infiltrate tissues, and expose immunostimulatory molecules in systemic lupus erythematosus.J Immunol. 2011; 187: 538-552
- Neutrophils activate plasmacytoid dendritic cells by releasing self-DNA-peptide complexes in systemic lupus erythematosus.Sci Transl Med. 2011; 3: 73ra19
- Neutrophil extracellular trap-associated protein activation of the NLRP3 inflammasome is enhanced in lupus macrophages.J Immunol. 2013; 190: 1217-1226
- Role of DNA/RNA sensors and contribution to autoimmunity.Cytokine Growth Factor Rev. 2014; 25: 745-757
- Epigallocatechin-3-gallate prevents lupus nephritis development in mice via enhancing the Nrf2 antioxidant pathway and inhibiting NLRP3 inflammasome activation.Free Radic Biol Med. 2011; 51: 744-754
- A novel antagonist of toll-like receptors 7, 8 and 9 suppresses lupus disease-associated parameters in NZBW/F1 mice.Autoimmunity. 2013; 46: 419-428
- Bay11-7082 attenuates murine lupus nephritis via inhibiting NLRP3 inflammasome and NF-κB activation.Int Immunopharmacol. 2013; 17: 116-122
- P2X7 blockade attenuates murine lupus nephritis by inhibiting activation of the NLRP3/ASC/caspase 1 pathway.Arthritis Rheum. 2013; 65: 3176-3185
- An essential role for caspase-1 in the induction of murine lupus and its associated vascular damage.Arthritis Rheum. 2014; 66: 153-162
- High mobility group box 1 inhibition alleviates lupus-like disease in BXSB mice.Scand J Immunol. 2014; 79: 333-337
- AIM2 facilitates the apoptotic DNA-induced systemic lupus erythematosus via arbitrating macrophage functional maturation.J Clin Immunol. 2013; 33: 925-937
- Molecular mechanism for p202-mediated specific inhibition of AIM2 inflammasome activation.Cell Rep. 2013; 4: 327-339
- Aim2 deficiency stimulates the expression of IFN-inducible Ifi202, a lupus susceptibility murine gene within the Nba2 autoimmune susceptibility locus.J Immunol. 2010; 185: 7385-7393
- Viral 5′-triphosphate RNA and non-CpG DNA aggravate autoimmunity and lupus nephritis via distinct TLR-independent immune responses.Eur J Immunol. 2008; 38: 3487-3498
- IL-1 beta-deficient mice are resistant to induction of experimental SLE.Eur Cytokine Netw. 2006; 17: 109-116
- Engagement of CD14 mediates the inflammatory potential of monosodium urate crystals.J Immunol. 2006; 177: 6370-6378
- Targeting transcription factor Stat4 uncovers a role for interleukin-18 in the pathogenesis of severe lupus nephritis in mice.Kidney Int. 2011; 79: 452-463
- Blockade of IL-18 receptor signaling delays the onset of autoimmune disease in MRL-Faslpr Mice.J Immunol. 2004; 173: 5312-5318
- Antroquinonol differentially modulates T cell activity and reduces interleukin-18 production, but enhances Nrf2 activation, in murine accelerated severe lupus nephritis.Arthritis Rheum. 2012; 64: 232-242
- Chloroquine treatment influences proinflammatory cytokine levels in systemic lupus erythematosus patients.Lupus. 2006; 15: 268-275
- Comparative effects of n-3, n-6 and n-9 unsaturated fatty acid-rich diet consumption on lupus nephritis, autoantibody production and CD4+ T cell-related gene responses in the autoimmune NZBWF1 mouse.PLoS One. 2014; 9: e100255
- Concentrated fish oil (Lovaza(R)) extends lifespan and attenuates kidney disease in lupus-prone short-lived (NZBxNZW)F1 mice.Exp Biol Med (Maywood). 2013; 238: 610-622
- Omega-3 in SLE: a double-blind, placebo-controlled randomized clinical trial of endothelial dysfunction and disease activity in systemic lupus erythematosus.Rheumatol Int. 2013; 33: 2789-2796
- A randomised interventional trial of omega-3-polyunsaturated fatty acids on endothelial function and disease activity in systemic lupus erythematosus.Ann Rheum Dis. 2008; 67: 841-848
- Inflammasomes are important mediators of cyclophosphamide-induced bladder inflammation.Am J Physiol Renal Physiol. 2014; 306: F299-F308
- Cytokines as biomarkers in rheumatoid arthritis.Mediators Inflamm. 2014; 2014: 545493
- Association of socioeconomic status with treatment delays, disease activity, joint damage and disability in rheumatoid arthritis.Arthritis Care Res. 2015; 67: 940-946
- Negative regulation of the NLRP3 inflammasome by A20 protects against arthritis.Nature. 2014; 512: 69-73
- Inhibition of P2X4 suppresses joint inflammation and damage in collagen-induced arthritis.Inflammation. 2014; 37: 146-153
- Inflammasome-independent role of apoptosis-associated speck-like protein containing a CARD (ASC) in T cell priming is critical for collagen-induced arthritis.J Biol Chem. 2010; 285: 12454-12462
- Inflammatory arthritis in caspase 1 gene-deficient mice: contribution of proteinase 3 to caspase 1-independent production of bioactive interleukin-1beta.Arthritis Rheum. 2009; 60: 3651-3662
- Evidence of NLRP3-inflammasome activation in rheumatoid arthritis (RA); genetic variants within the NLRP3-inflammasome complex in relation to susceptibility to RA and response to anti-TNF treatment.Ann Rheum Dis. 2014; 73: 1202-1210
- Expression and function of the NALP3 inflammasome in rheumatoid synovium.Immunology. 2010; 129: 178-185
- NLRP1 gene polymorphism influences gene transcription and is a risk factor for rheumatoid arthritis in han chinese.Arthritis Rheum. 2012; 64: 647-654
- Genetic variation in proteins of the cryopyrin inflammasome influences susceptibility and severity of rheumatoid arthritis (the Swedish TIRA project).Rheumatology (Oxford). 2008; 47: 415-417
- Anti-TNF treatment response in rheumatoid arthritis patients is associated with genetic variation in the NLRP3-inflammasome.PLoS One. 2014; 9: e100361
- Association of IL-18 promoter gene polymorphisms with rheumatoid arthritis: a meta-analysis.Mol Biol Rep. 2014; 41: 8211-8217
- IL-18 upregulates the production of key regulators of osteoclastogenesis from fibroblast-like synoviocytes in rheumatoid arthritis.Inflammation. 2013; 36: 103-109
- Interleukin 18 induces angiogenesis in vitro and in vivo via Src and Jnk kinases.Ann Rheum Dis. 2010; 69: 2204-2212
- Interleukin-18 as an in vivo mediator of monocyte recruitment in rodent models of rheumatoid arthritis.Arthritis Res Ther. 2010; 12: R118
- The roles of interleukin-18 in collagen-induced arthritis in the BB rat.Clin Exp Immunol. 2004; 136: 440-447
- The use of anakinra, an interleukin-1 receptor antagonist, in the treatment of rheumatoid arthritis.Rheum Dis Clin North Am. 2004; 30 (vii): 365-380
- Efficacy and safety of the human anti-IL-1beta monoclonal antibody canakinumab in rheumatoid arthritis: results of a 12-week, phase II, dose-finding study.BMC Musculoskelet Disord. 2011; 12: 153
- Fish oil in recent onset rheumatoid arthritis: a randomised, double-blind controlled trial within algorithm-based drug use.Ann Rheum Dis. 2015; 74: 89-95
- Long-term intake of dietary long-chain n-3 polyunsaturated fatty acids and risk of rheumatoid arthritis: a prospective cohort study of women.Ann Rheum Dis. 2014; 73: 1949-1953
- Selective Interleukin-1b converting enzyme (ICE/Caspase-1) inhibition with pralnacasan.Arthritis Rheum Suppl. 2001; (abstract #1134)
- Genetic variants in CARD8 but not in NLRP3 are associated with ankylosing spondylitis.Scand J Rheumatol. 2013; 42: 465-468
- Thalidomide reduces recurrence of ankylosing spondylitis in patients following discontinuation of etanercept.Rheumatol Int. 2013; 33: 1409-1413
- International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001.J Rheumatol. 2004; 31: 390-392
- Epidemiology of juvenile idiopathic arthritis in Alsace, France.J Rheumatol. 2006; 33: 1377-1381
- Evaluation of the presentation of systemic onset juvenile rheumatoid arthritis: data from the Pennsylvania Systemic Onset Juvenile Arthritis Registry (PASOJAR).J Rheumatol. 2008; 35: 343-348
- Early predictors of poor functional outcome in systemic-onset juvenile rheumatoid arthritis: a multicenter cohort study.Arthritis Rheum. 2000; 43: 2402-2409
- Macrophage activation syndrome: a potentially fatal complication of rheumatic disorders.Arch Dis Child. 2001; 85: 421-426
- Adult-onset Still's disease-pathogenesis, clinical manifestations, and new treatment options.Ann Med. 2015; 47: 6-14
- Association of NLRP3 and CARD8 genetic polymorphisms with juvenile idiopathic arthritis in a Taiwanese population.Scand J Rheumatol. 2014; 43: 146-152
- Role of interleukin-1 (IL-1) in the pathogenesis of systemic onset juvenile idiopathic arthritis and clinical response to IL-1 blockade.J Exp Med. 2005; 201: 1479-1486
- Gene expression profiling of peripheral blood from patients with untreated new-onset systemic juvenile idiopathic arthritis reveals molecular heterogeneity that may predict macrophage activation syndrome.Arthritis Rheum. 2007; 56: 3793-3804
- Specific gene expression profiles in systemic juvenile idiopathic arthritis.Arthritis Rheum. 2007; 56: 1954-1965
- Blood and synovial fluid cytokine signatures in patients with juvenile idiopathic arthritis: a cross-sectional study.Ann Rheum Dis. 2007; 66: 589-598
- Interleukin 18 as a marker of disease activity and severity in patients with juvenile idiopathic arthritis.J Rheumatol. 2007; 34: 823-830
- Distinct subsets of patients with systemic juvenile idiopathic arthritis based on their cytokine profiles.Cytokine. 2013; 61: 345-348
- Effective use of the recombinant interleukin 1 receptor antagonist anakinra in therapy resistant systemic onset juvenile rheumatoid arthritis.J Rheumatol. 2004; 31: 2071-2075
- A multicentre, randomised, double-blind, placebo-controlled trial with the interleukin-1 receptor antagonist anakinra in patients with systemic-onset juvenile idiopathic arthritis (ANAJIS trial).Ann Rheum Dis. 2011; 70: 747-754
- Anakinra as first-line disease-modifying therapy in systemic juvenile idiopathic arthritis: report of forty-six patients from an international multicenter series.Arthritis Rheum. 2011; 63: 545-555
- Efficacy and long-term follow-up of IL-1R inhibitor anakinra in adults with Still's disease: a case-series study.Arthritis Res Ther. 2011; 13: R91
- Two randomized trials of canakinumab in systemic juvenile idiopathic arthritis.N Engl J Med. 2012; 367: 2396-2406
- The use of canakinumab, a novel IL-1beta long-acting inhibitor, in refractory adult-onset Still's disease.Semin Arthritis Rheum. 2012; 42: 201-205
- IL-1 Trap rilonacept in refractory adult onset Still's disease.Ann Rheum Dis. 2012; 71: 2056-2057
- Randomized, double-blind, placebo-controlled trial of the efficacy and safety of rilonacept in the treatment of systemic juvenile idiopathic arthritis.Arthritis Rheumatol. 2014; 66: 2570-2579
- An inherited mutation in NLRC4 causes autoinflammation in human and mice.J Exp Med. 2014; 211: 2385-2396
- Mutation of NLRC4 causes a syndrome of enterocolitis and autoinflammation.Nat Genet. 2014; 46: 1135-1139
- Monogenic IL-1 mediated autoinflammatory and immunodeficiency syndromes: finding the right balance in response to danger signals.Clin Immunol. 2010; 135: 210-222
- De novo CIAS1 mutations, cytokine activation, and evidence for genetic heterogeneity in patients with neonatal-onset multisystem inflammatory disease (NOMID): a new member of the expanding family of pyrin-associated autoinflammatory diseases.Arthritis Rheum. 2002; 46: 3340-3348
- Clinical and genetic heterogeneity among Spanish patients with recurrent autoinflammatory syndromes associated with the CIAS1/PYPAF1/NALP3 gene.Arthritis Rheum. 2004; 50: 4045-4050
- Neonatal-onset multisystem inflammatory disease responsive to interleukin-1beta inhibition.N Engl J Med. 2006; 355: 581-592
- An autoinflammatory disease due to homozygous deletion of the IL1RN locus.N Engl J Med. 2009; 360: 2438-2444
- An autoinflammatory disease with deficiency of the interleukin-1-receptor antagonist.N Engl J Med. 2009; 360: 2426-2437
- Ancient missense mutations in a new member of the RoRet gene family are likely to cause familial Mediterranean fever. The International FMF Consortium.Cell. 1997; 90: 797-807
- The inflammasome—a linebacker of innate defense.N Engl J Med. 2006; 355: 730-732
- Familial Mediterranean fever—a not so unusual cause of abdominal pain.Best Pract Res Clin Gastroenterol. 2005; 19: 199-213
- Familial Mediterranean fever.Lancet. 1998; 351: 659-664
- Ethnic distribution and amyloidosis in familial Mediterranean fever (FMF).Pathol Microbiol. 1961; 24: 718-723
- Familial Mediterranean fever (FMF) in Turkey: results of a nationwide multicenter study.Medicine. 2005; 84: 1-11
- Novel therapeutics for the treatment of familial Mediterranean fever: from colchicine to biologics.Clin Pharmacol Ther. 2014; 95: 89-97
- Mutations in MVK, encoding mevalonate kinase, cause hyperimmunoglobulinaemia D and periodic fever syndrome.Nat Genet. 1999; 22: 175-177
- Cutaneous manifestations and histologic findings in the hyperimmunoglobulinemia D syndrome. International Hyper IgD Study Group.Arch Dermatol. 1994; 130: 59-65
- Diagnostic value of serum immunoglobulinaemia D level in patients with a clinical suspicion of hyper IgD syndrome.Rheumatology (Oxford). 2007; 46: 1597-1600
- Mutations in CD2BP1 disrupt binding to PTP PEST and are responsible for PAPA syndrome, an autoinflammatory disorder.Hum Mol Genet. 2002; 11: 961-969
- Clinical, molecular, and genetic characteristics of PAPA syndrome: a review.Curr Genomics. 2010; 11: 519-527
- Germline mutations in the extracellular domains of the 55 kDa TNF receptor, TNFR1, define a family of dominantly inherited autoinflammatory syndromes.Cell. 1999; 97: 133-144
- Familial Hibernian fever.Q J Med. 1982; 51: 469-480
- The tumour necrosis factor receptor-associated periodic syndrome: current concepts.Expert Rev Mol Med. 2005; 7: 1-18
- TNF receptor-associated periodic syndrome (TRAPS): description of a novel TNFRSF1A mutation and response to etanercept.Eur J Pediatr. 2008; 167: 1421-1425
- Severe TNF receptor-associated periodic syndrome due to 2 TNFRSF1A mutations including a new F60V substitution.Gastroenterology. 2006; 130: 172-178
- Inflammasome and cytokine blocking strategies in autoinflammatory disorders.Clin Immunol. 2013; 147: 242-275
- Colchicine: 1998 update.Semin Arthritis Rheum. 1998; 28: 48-59
- Successful treatment of familial Mediterranean fever with anakinra and outcome after renal transplantation.Nephrol Dial Transplant. 2009; 24: 676-678
- Rilonacept for colchicine-resistant or -intolerant familial Mediterranean fever: a randomized trial.Ann Intern Med. 2012; 157: 533-541
- On-demand anakinra treatment is effective in mevalonate kinase deficiency.Ann Rheum Dis. 2011; 70: 2155-2158
- Treatment of hyperimmunoglobulinemia D syndrome with biologics in children: review of the literature and Finnish experience.Eur J Pediatr. 2015; 174: 707-714
- Osteolytic lesion in PAPA syndrome responding to anti-interleukin 1 treatment.J Rheumatol. 2014; 41: 2333-2334
- Efficacy of etanercept in the tumor necrosis factor receptor-associated periodic syndrome: a prospective, open-label, dose-escalation study.Arthritis Rheum. 2012; 64: 908-913
- Failure of anti-TNF therapy in TNF receptor 1-associated periodic syndrome (TRAPS).Rheumatology (Oxford). 2007; 46: 1211-1212
- Persistent efficacy of anakinra in patients with tumor necrosis factor receptor-associated periodic syndrome.Arthritis Rheum. 2008; 58: 1516-1520
- Dramatic improvement following interleukin 1beta blockade in tumor necrosis factor receptor-1-associated syndrome (TRAPS) resistant to anti-TNF-alpha therapy.J Rheumatol. 2008; 35: 357-358
- Prevalence of gout and hyperuricemia in the US general population: the National Health and Nutrition Examination Survey 2007-2008.Arthritis Rheum. 2011; 63: 3136-3141
- Epidemiology of gout: is the incidence rising?.J Rheumatol. 2002; 29: 2403-2406
- Osteoarthritis and articular chondrocalcinosis in the elderly.Ann Rheum Dis. 1983; 42: 280-284
- Innate immunity conferred by toll-like receptors 2 and 4 and myeloid differentiation factor 88 expression is pivotal to monosodium urate monohydrate crystal-induced inflammation.Arthritis Rheum. 2005; 52: 2936-2946
- Engagement of fatty acids with toll-like receptor 2 drives interleukin-1beta production via the ASC/caspase 1 pathway in monosodium urate monohydrate crystal-induced gouty arthritis.Arthritis Rheum. 2010; 62: 3237-3248
- Receptor-independent, direct membrane binding leads to cell-surface lipid sorting and Syk kinase activation in dendritic cells.Immunity. 2008; 29: 807-818
- Gout-associated uric acid crystals activate the NALP3 inflammasome.Nature. 2006; 440: 237-241
- Signaling by ROS drives inflammasome activation.Eur J Immunol. 2010; 40: 616-619
- Thioredoxin-interacting protein links oxidative stress to inflammasome activation.Nat Immunol. 2010; 11: 136-140
- Malarial hemozoin is a Nalp3 inflammasome activating danger signal.PLoS One. 2009; 4: e6510
- Enhanced p62 expression through impaired proteasomal degradation is involved in caspase-1 activation in monosodium urate crystal-induced interleukin-1b expression.Rheumatology (Oxford). 2014; 53: 1043-1053
- Caspase 1-independent activation of interleukin-1beta in neutrophil-predominant inflammation.Arthritis Rheum. 2009; 60: 3642-3650
- Pathogenic role of basic calcium phosphate crystals in destructive arthropathies.PLoS One. 2013; 8: e57352
- Cholesterol crystals activate the NLRP3 inflammasome in human macrophages: a novel link between cholesterol metabolism and inflammation.PLoS One. 2010; 5: e11765
- Mitochondrial control of the NLRP3 inflammasome.Nat Immunol. 2011; 12: 199-200
- A role for mitochondria in NLRP3 inflammasome activation.Nature. 2011; 469: 221-225
- Cutting edge: reactive oxygen species inhibitors block priming, but not activation, of the NLRP3 inflammasome.J Immunol. 2011; 187: 613-617
- Prostaglandins and inflammation.Arterioscler Thromb Vasc Biol. 2011; 31: 986-1000
- AMP-activated protein kinase suppresses urate crystal-induced inflammation and transduces colchicine effects in macrophages.Ann Rheum Dis. 2014; ([Epub ahead of print])
- A pilot study of IL-1 inhibition by anakinra in acute gout.Arthritis Res Ther. 2007; 9: R28
- Treatment of acute gouty arthritis in complex hospitalized patients with anakinra.Arthritis Care Res (Hoboken). 2013; 65: 1381-1384
- Efficacy of anakinra in gouty arthritis: a retrospective study of 40 cases.Arthritis Res Ther. 2013; 15: R123
- Anakinra's efficacy is variable in refractory gout: report of ten cases.Semin Arthritis Rheum. 2010; 40: 210-214
- Rilonacept in the treatment of acute gouty arthritis: a randomized, controlled clinical trial using indomethacin as the active comparator.Arthritis Res Ther. 2013; 15: R25
- The interleukin 1 inhibitor rilonacept in treatment of chronic gouty arthritis: results of a placebo-controlled, monosequence crossover, non-randomised, single-blind pilot study.Ann Rheum Dis. 2009; 68: 1613-1617
- Rilonacept for gout flare prevention during initiation of uric acid-lowering therapy: results from the PRESURGE-2 international, phase 3, randomized, placebo-controlled trial.Rheumatology (Oxford). 2013; 52: 1285-1292
- Rilonacept (interleukin-1 trap) for prevention of gout flares during initiation of uric acid-lowering therapy: results from a phase III randomized, double-blind, placebo-controlled, confirmatory efficacy study.Arthritis Care Res (Hoboken). 2012; 64: 1462-1470
- Canakinumab for the treatment of acute flares in difficult-to-treat gouty arthritis: results of a multicenter, phase II, dose-ranging study.Arthritis Rheum. 2010; 62: 3064-3076
- Canakinumab relieves symptoms of acute flares and improves health-related quality of life in patients with difficult-to-treat gouty arthritis by suppressing inflammation: results of a randomized, dose-ranging study.Arthritis Res Ther. 2011; 13: R53
- Canakinumab reduces the risk of acute gouty arthritis flares during initiation of allopurinol treatment: results of a double-blind, randomised study.Ann Rheum Dis. 2011; 70: 1264-1271
- Anakinra is a possible alternative in the treatment and prevention of acute attacks of pseudogout in end-stage renal failure.Joint Bone Spine. 2009; 76: 424-426
- Efficacy of anakinra in calcium pyrophosphate crystal-induced arthritis: a report of 16 cases and review of the literature.Joint Bone Spine. 2013; 80: 178-182
- Efficacy of anakinra in articular chondrocalcinosis: report of three cases.Joint Bone Spine. 2012; 79: 330-331
- EULAR recommendations for calcium pyrophosphate deposition. Part II: management.Ann Rheum Dis. 2011; 70: 571-575
Article info
Publication history
Published online: June 10, 2015
Accepted:
June 4,
2015
Received in revised form:
June 2,
2015
Received:
March 13,
2015
Footnotes
Sara S. McCoy and Jasmine Stannard contributed equally to this work.
Identification
Copyright
© 2016 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
