Evasion of inflammasome activation by microbial pathogens

Journal of Clinical Investigation

Volumn 125, Issue 2, 2015, Pages 469-477

  Ulland, Tyler K ^a   Ferguson, Polly J ^b   Sutterwala, Fayyaz S ^a,b,c  

^a UNIVERSITY OF IOWA   (United States)

^b UNIVERSITY OF IOWA   (United States)

^c VETERANS AFFAIRS MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CANAKINUMAB; CASPASE 11; CASPASE 4; CASPASE 5; GEVOKIZUMAB; INFLAMMASOME; INTERLEUKIN 1; LIPID A; LIPOPOLYSACCHARIDE; RECOMBINANT INTERLEUKIN 1 RECEPTOR BLOCKING AGENT; RILONACEPT; IL1B PROTEIN, HUMAN; INTERLEUKIN 18; INTERLEUKIN 18 PROTEIN, HUMAN; INTERLEUKIN 1BETA;

ADAPTIVE IMMUNITY; CELL DEATH; DRUG SAFETY; EFFECTOR CELL; GASTROINTESTINAL SYMPTOM; HUMAN; IMMUNE EVASION; INFECTIOUS COMPLICATION; INJECTION SITE REACTION; LIGAND BINDING; MICROBIAL ACTIVITY; NONHUMAN; OUTCOME ASSESSMENT; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN BINDING; REVIEW; UPPER RESPIRATORY TRACT INFECTION; ANIMAL; IMMUNOLOGY; INFECTION; INFLAMMATION; PATHOLOGY;

ANIMALS; CELL DEATH; HUMANS; IMMUNE EVASION; INFECTION; INFLAMMASOMES; INFLAMMATION; INTERLEUKIN-18; INTERLEUKIN-1BETA;

EID: 84961290279     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI75254     Document Type: Review

References (113)

1. Schroder K, Tschopp J. The inflammasomes. Cell. 2010;140(6):821-832.
2. Lamkanfi M, Dixit VM. Mechanisms and functions of inflammasomes. Cell. 2014;157(5):1013-1022.
3. von Moltke J, et al. Rapid induction of inflammatory lipid mediators by the inflammasome in vivo. Nature. 2012;490(7418):107-111.
4. Elinav E, et al. NLRP6 inflammasome regulates colonic microbial ecology and risk for colitis. Cell. 2011;145(5):745-757.
5. Khare S, et al. An NLRP7-containing inflammasome mediates recognition of microbial lipopeptides in human macrophages. Immunity. 2012;36(3):464-476.
6. Poeck H, et al. Recognition of RNA virus by RIG-I results in activation of CARD9 and inflammasome signaling for interleukin 1β production. Nat Immunol. 2010;11(1):63-69.
7. Kerur N, et al. IFI16 acts as a nuclear pathogen sensor to induce the inflammasome in response to Kaposi Sarcoma-associated herpesvirus infection. Cell Host Microbe. 2011;9(5):363-375.
8. Chae JJ, et al. Gain-of-function Pyrin mutations induce NLRP3 protein-independent interleukin-1β activation and severe autoinflammation in mice. Immunity. 2011;34(5):755-768.
9. Seshadri S, Duncan MD, Hart JM, Gavrilin MA, Wewers MD. Pyrin levels in human monocytes and monocyte-derived macrophages regulate IL-1β processing and release. J Immunol. 2007;179(2):1274-1281.
10. Yu JW, et al. Cryopyrin and pyrin activate caspase-1, but not NF-κB, via ASC oligomerization. Cell Death Differ. 2006;13(2):236-249.
11. Xu H, et al. Innate immune sensing of bacterial modifications of Rho GTPases by the Pyrin inflammasome. Nature. 2014;513(7517):237-241.
12. Kayagaki N, et al. Non-canonical inflammasome activation targets caspase-11. Nature. 2011;479(7371):117-121.
13. Kayagaki N, et al. Noncanonical inflammasome activation by intracellular LPS independent of TLR4. Science. 2013;341(6151):1246-1249.
14. Hagar JA, Powell DA, Aachoui Y, Ernst RK, Miao EA. Cytoplasmic LPS activates caspase-11: implications in TLR4-independent endotoxic shock. Science. 2013;341(6151):1250-1253.
15. Shi J, et al. Inflammatory caspases are innate immune receptors for intracellular LPS. Nature. 2014;514(7521):187-192.
16. Boyden ED, Dietrich WF. Nalp1b controls mouse macrophage susceptibility to anthrax lethal toxin. Nat Genet. 2006;38(2):240-244.
17. Terra JK, et al. Cutting edge: resistance to Bacillus anthracis infection mediated by a lethal toxin sensitive allele of Nalp1b/Nlrp1b. J Immunol. 2010;184(1):17-20.
18. Ewald SE, Chavarria-Smith J, Boothroyd JC. NLRP1 is an inflammasome sensor for Toxoplasma gondii. Infect Immun. 2014;82(1):460-468.
19. Gorfu G, et al. Dual role for inflammasome sensors NLRP1 and NLRP3 in murine resistance to Toxoplasma gondii. MBio. 2014;5(1):e01117-13.
20. Sutterwala FS, Haasken S, Cassel SL. Mechanism of NLRP3 inflammasome activation. Ann N Y Acad Sci. 2014;1319(1):82-95.
21. Vladimer GI, Marty-Roix R, Ghosh S, Weng D, Lien E. Inflammasomes and host defenses against bacterial infections. Curr Opin Microbiol. 2013;16(1):23-31.
22. Joly S, Sutterwala FS. Fungal pathogen recognition by the NLRP3 inflammasome. Virulence. 2010;1(4):276-280.
23. Lupfer C, Kanneganti TD. The expanding role of NLRs in antiviral immunity. Immunol Rev. 2013;255(1):13-24.
24. Clay GM, Sutterwala FS, Wilson ME. NLR proteins parasitic disease. Immunol Res. 2014;59(1-3):142-152.
25. Nakahira K, et al. Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome. Nat Immunol. 2011;12(3):222-230.
26. Iyer SS, et al. Mitochondrial cardiolipin is required for Nlrp3 inflammasome activation. Immunity. 2013;39(2):311-323.
27. Gong YN, Shao F. Sensing bacterial infections by NAIP receptors in NLRC4 inflammasome activation. Protein Cell. 2012;3(2):98-105.
28. Schattgen SA, Fitzgerald KA. The PYHIN protein family as mediators of host defenses. Immunol Rev. 2011;243(1):109-118.
29. Broz P, Newton K, Lamkanfi M, Mariathasan S, Dixit VM, Monack DM. Redundant roles for inflammasome receptors NLRP3 and NLRC4 in host defense against Salmonella. J Exp Med. 2010;207(8):1745-1755.
30. Miao EA, et al. Innate immune detection of the type III secretion apparatus through the NLRC4 inflammasome. Proc Natl Acad Sci U S A. 2010;107(7):3076-3080.
31. Miao EA, et al. Cytoplasmic flagellin activates caspase-1 and secretion of interleukin 1β via Ipaf. Nat Immunol. 2006;7(6):569-575.
32. Franchi L, et al. Cytosolic flagellin requires Ipaf for activation of caspase-1 and interleukin 1β in salmonella-infected macrophages. Nat Immunol. 2006;7(6):576-582.
33. Ibarra JA, Steele-Mortimer O. Salmonella - the ultimate insider. Salmonella virulence factors that modulate intracellular survival. Cell Microbiol. 2009;11(11):1579-1586.
34. Wynosky-Dolfi MA, et al. Oxidative metabolism enables Salmonella evasion of the NLRP3 inflammasome. J Exp Med. 2014;211(4):653-668.
35. Higa N, et al. Vibrio parahaemolyticus effector proteins suppress inflammasome activation by interfering with host autophagy signaling. PLoS Pathog. 2013;9(1):e1003142.
36. Sutterwala FS, Mijares LA, Li L, Ogura Y, Kazmierczak BI, Flavell RA. Immune recognition of Pseudomonas aeruginosa mediated by the IPAF/NLRC4 inflammasome. J Exp Med. 2007;204(13):3235-3245.
37. Galle M, et al. The Pseudomonas aeruginosa Type III secretion system plays a dual role in the regulation of caspase-1 mediated IL-1beta maturation. J Cell Mol Med. 2008;12(5 A):1767-1776.
38. Brodsky IE, et al. A Yersinia effector protein promotes virulence by preventing inflammasome recognition of the type III secretion system. Cell Host Microbe. 2010;7(5):376-387.
39. LaRock CN, Cookson BT. The Yersinia virulence effector YopM binds caspase-1 to arrest inflammasome assembly and processing. Cell Host Microbe. 2012;12(6):799-805.
40. Schotte P, Denecker G, Van Den Broeke A, Vandenabeele P, Cornelis GR, Beyaert R. Targeting Rac1 by the Yersinia effector protein YopE inhibits caspase-1-mediated maturation and release of interleukin-1β. J Biol Chem. 2004;279(24):25134-25142.
41. Feltman H, Schulert G, Khan S, Jain M, Peterson L, Hauser AR. Prevalence of type III secretion genes in clinical and environmental isolates of Pseudomonas aeruginosa. Microbiology. 2001;147(pt 10):2659-2669.
42. Trulzsch K, Sporleder T, Igwe EI, Russmann H, Heesemann J. Contribution of the major secreted yops of Yersinia enterocolitica O:8 to pathogenicity in the mouse infection model. Infect Immun. 2004;72(9):5227-5234.
43. Sauer JD, Witte CE, Zemansky J, Hanson B, Lauer P, Portnoy DA. Listeria monocytogenes triggers AIM2-mediated pyroptosis upon infrequent bacteriolysis in the macrophage cytosol. Cell Host Microbe. 2010;7(5):412-419.
44. Fernandes-Alnemri T, et al. The AIM2 inflammasome is critical for innate immunity to Francisella tularensis. Nat Immunol. 2010;11(5):385-393.
45. Jones JW, et al. Absent in melanoma 2 is required for innate immune recognition of Francisella tularensis. Proc Natl Acad Sci U S A. 2010;107(21):9771-9776.
46. Ulland TK, et al. Cutting edge: mutation of Francisella tularensis mviN leads to increased macrophage absent in melanoma 2 inflammasome activation and a loss of virulence. J Immunol. 2010;185(5):2670-2674.
47. Peng K, Broz P, Jones J, Joubert LM, Monack D. Elevated AIM2-mediated pyroptosis triggered by hypercytotoxic Francisella mutant strains is attributed to increased intracellular bacteriolysis. Cell Microbiol. 2011;13(10):1586-1600.
48. Huang MT, et al. Deletion of ripA alleviates suppression of the inflammasome and MAPK by Francisella tularensis. J Immunol. 2010;185(9):5476-5485.
49. Jayakar HR, et al. A galU mutant of Francisella tularensis is attenuated for virulence in a murine pulmonary model of tularemia. BMC Microbiol. 2011;11:179.
50. Weiss DS, Brotcke A, Henry T, Margolis JJ, Chan K, Monack DM. In vivo negative selection screen identifies genes required for Francisella virulence. Proc Natl Acad Sci U S A. 2007;104(14):6037-6042.
51. Dotson RJ, et al. Repression of inflammasome by Francisella tularensis during early stages of infection. J Biol Chem. 2013;288(33):23844-23857.
52. Ge J, Gong YN, Xu Y, Shao F. Preventing bacterial DNA release and absent in melanoma 2 inflammasome activation by a Legionella effector functioning in membrane trafficking. Proc Natl Acad Sci U S A. 2012;109(16):6193-6198.
53. Shah S, et al. Cutting edge: Mycobacterium tuberculosis but not nonvirulent mycobacteria inhibits IFN-β and AIM2 inflammasome-dependent IL-1β production via its ESX-1 secretion system. J Immunol. 2013;191(7):3514-3518.
54. Henry T, Brotcke A, Weiss DS, Thompson LJ, Monack DM. Type I interferon signaling is required for activation of the inflammasome during Francisella infection. J Exp Med. 2007;204(5):987-994.
55. Gregory SM, et al. Discovery of a viral NLR homolog that inhibits the inflammasome. Science. 2011;331(6015):330-334.
56. Johnston JB, et al. A poxvirus-encoded pyrin domain protein interacts with ASC-1 to inhibit host inflammatory and apoptotic responses to infection. Immunity. 2005;23(6):587-598.
57. Best SM. Viral subversion of apoptotic enzymes: escape from death row. Annu Rev Microbiol. 2008;62:171-192.
58. Ray CA, et al. Viral inhibition of inflammation: cowpox virus encodes an inhibitor of the interleukin-1β converting enzyme. Cell. 1992;69(4):597-604.
59. Swanson R, Raghavendra MP, Zhang W, Froelich C, Gettins PG, Olson ST. Serine and cysteine proteases are translocated to similar extents upon formation of covalent complexes with serpins. Fluorescence perturbation and fluorescence resonance energy transfer mapping of the protease binding site in CrmA complexes with granzyme B and caspase-1. J Biol Chem. 2007;282(4):2305-2313.
60. Fellermann K. Adverse events of tumor necrosis factor inhibitors. Dig Dis. 2013;31(3-4):374-378.
61. Keane J, et al. Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. N Engl J Med. 2001;345(15):1098-1104.
62. Opal SM, et al. Confirmatory interleukin-1 receptor antagonist trial in severe sepsis: a phase III, randomized, double-blind, placebo-controlled, multicenter trial. The Interleukin-1 Receptor Antagonist Sepsis Investigator Group. Crit Care Med. 1997;25(7):1115-1124.
63. Fisher CJ Jr, et al. Recombinant human interleukin 1 receptor antagonist in the treatment of patients with sepsis syndrome. Results from a randomized, double-blind, placebo-controlled trial. Phase III rhIL-1ra Sepsis Syndrome Study Group. JAMA. 1994;271(23):1836-1843.
64. Fisher CJ Jr, et al. Initial evaluation of human recombinant interleukin-1 receptor antagonist in the treatment of sepsis syndrome: a randomized, open-label, placebo-controlled multicenter trial. Crit Care Med. 1994;22(1):12-21.
65. Marshall JC. Such stuff as dreams are made on: mediator-directed therapy in sepsis. Nat Rev Drug Discov. 2003;2(5):391-405.
66. Campion GV, Lebsack ME, Lookabaugh J, Gordon G, Catalano M. Dose-range and dosefrequency study of recombinant human interleukin-1 receptor antagonist in patients with rheumatoid arthritis. The IL-1Ra Arthritis Study Group. Arthritis Rheum. 1996;39(7):1092-1101.
67. Bresnihan B, et al. Treatment of rheumatoid arthritis with recombinant human interleukin-1 receptor antagonist. Arthritis Rheum. 1998;41(12):2196-2204.
68. Nuki G, et al. Long-term safety and maintenance of clinical improvement following treatment with anakinra (recombinant human interleukin-1 receptor antagonist) in patients with rheumatoid arthritis: extension phase of a randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2002;46(11):2838-2846.
69. Cohen S, et al. Treatment of rheumatoid arthritis with anakinra, a recombinant human interleukin-1 receptor antagonist, in combination with methotrexate: results of a twenty-fourweek, multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2002;46(3):614-624.
70. Fleischmann RM, et al. Anakinra, a recombinant human interleukin-1 receptor antagonist (r-metHuIL-1ra), in patients with rheumatoid arthritis: A large, international, multicenter, placebo-controlled trial. Arthritis Rheum. 2003;48(4):927-934.
71. Cohen SB, et al. A multicentre, double blind, randomised, placebo controlled trial of anakinra (Kineret), a recombinant interleukin 1 receptor antagonist, in patients with rheumatoid arthritis treated with background methotrexate. Ann Rheum Dis. 2004;63(9):1062-1068.
72. Fleischmann RM, et al. Safety of extended treatment with anakinra in patients with rheumatoid arthritis. Ann Rheum Dis. 2006;65(8):1006-1012.
73. Genovese MC, et al. Combination therapy with etanercept and anakinra in the treatment of patients with rheumatoid arthritis who have been treated unsuccessfully with methotrexate. Arthritis Rheum. 2004;50(5):1412-1419.
74. Sibley CH, et al. Sustained response and prevention of damage progression in patients with neonatal-onset multisystem inflammatory disease treated with anakinra: a cohort study to determine three- and five-year outcomes. Arthritis Rheum. 2012;64(7):2375-2386.
75. Almeida de Jesus A, Goldbach-Mansky R. Monogenic autoinflammatory diseases: concept and clinical manifestations. Clin Immunol. 2013;147(3):155-174.
76. Pascual V, Allantaz F, Arce E, Punaro M, Banchereau J. 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(9):1479-1486.
77. Verbsky JW, White AJ. Effective use of the recombinant interleukin 1 receptor antagonist anakinra in therapy resistant systemic onset juvenile rheumatoid arthritis. J Rheumatol. 2004;31(10):2071-2075.
78. Fitzgerald AA, Leclercq SA, Yan A, Homik JE, Dinarello CA. Rapid responses to anakinra in patients with refractory adult-onset Still's disease. Arthritis Rheum. 2005;52(6):1794-1803.
79. Lequerre T, et al. Interleukin-1 receptor antagonist (anakinra) treatment in patients with systemic-onset juvenile idiopathic arthritis or adult onset Still disease: preliminary experience in France. Ann Rheum Dis. 2008;67(3):302-308.
80. So A, De Smedt T, Revaz S, Tschopp J. A pilot study of IL-1 inhibition by anakinra in acute gout. Arthritis Res Ther. 2007;9(2):R28.
81. Ilowite N, et al. Anakinra in the treatment of polyarticular-course juvenile rheumatoid arthritis: safety and preliminary efficacy results of a randomized multicenter study. Clin Rheumatol. 2009;28(2):129-137.
82. Larsen CM, et al. Interleukin-1-receptor antagonist in type 2 diabetes mellitus. N Engl J Med. 2007;356(15):1517-1526.
83. Abbate A, et al. Effects of interleukin-1 blockade with anakinra on adverse cardiac remodeling and heart failure after acute myocardial infarction [from the Virginia Commonwealth University-Anakinra Remodeling Trial (2) (VCU-ART2) pilot study]. Am J Cardiol. 2013;111(10):1394-1400.
84. Ikonomidis I, et al. Inhibition of interleukin-1 by anakinra improves vascular and left ventricular function in patients with rheumatoid arthritis. Circulation. 2008;117(20):2662-2669.
85. Van Tassell BW, et al. Effects of interleukin-1 blockade with anakinra on aerobic exercise capacity in patients with heart failure and preserved ejection fraction (from the D-HART pilot study). Am J Cardiol. 2014;113(2):321-327.
86. van de Veerdonk FL, Netea MG, Dinarello CA, van der Meer JW. Anakinra for the inflammatory complications of chronic granulomatous disease. Neth J Med. 2011;69(2):95.
87. Dinarello CA, van der Meer JW. Treating inflammation by blocking interleukin-1 in humans. Semin Immunol. 2013;25(6):469-484.
88. Goldbach-Mansky R, et al. A pilot study to evaluate the safety and efficacy of the longacting interleukin-1 inhibitor rilonacept (interleukin-1 Trap) in patients with familial cold autoinflammatory syndrome. Arthritis Rheum. 2008;58(8):2432-2442.
89. Hoffman HM, et al. Efficacy and safety of rilonacept (interleukin-1 Trap) in patients with cryopyrin-associated periodic syndromes: results from two sequential placebo-controlled studies. Arthritis Rheum. 2008;58(8):2443-2452.
90. Hoffman HM, et al. Long-term efficacy and safety profile of rilonacept in the treatment of cryopryin-associated periodic syndromes: results of a 72-week open-label extension study. Clin Ther. 2012;34(10):2091-2103.
91. Terkeltaub R, et al. 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(10):1613-1617.
92. Schumacher HR Jr, et al. Rilonacept (interleukin-1 trap) in the prevention of acute gout flares during initiation of urate-lowering therapy: results of a phase II randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2012;64(3):876-884.
93. Ilowite NT, for the RAPPORT Investigators. Randomized, double-blind, placebo-controlled trial of the efficacy and safety of rilonacept in the treatment of systemic juvenile idiopathic arthritis [published online ahead of print December 15, 2014]. Arthritis Rheum. doi:10.1002/art.38991.
94. Lovell DJ, et al. Long-term safety and efficacy of rilonacept in patients with systemic juvenile idiopathic arthritis. Arthritis Rheum. 2013;65(9):2486-2496.
95. Petryna O, Cush JJ, Efthimiou P. IL-1 Trap rilonacept in refractory adult onset Still's disease. Ann Rheum Dis. 2012;71(12):2056-2057.
96. Hashkes PJ, et al. Rilonacept for colchicineresistant or -intolerant familial Mediterranean fever: a randomized trial. Ann Intern Med. 2012;157(8):533-541.
97. Krause K, et al. Efficacy and safety of the interleukin-1 antagonist rilonacept in Schnitzler syndrome: an open-label study. Allergy. 2012;67(7):943-950.
98. Kuemmerle-Deschner JB, et al. Canakinumab (ACZ885, a fully human IgG1 anti-IL-1beta mAb) induces sustained remission in pediatric patients with cryopyrin-associated periodic syndrome (CAPS). Arthritis Res Ther. 2011;13(1):R34.
99. Cavelti-Weder C, et al. Effects of gevokizumab on glycemia and inflammatory markers in type 2 diabetes. Diabetes Care. 2012;35(8):1654-1662.
100. Kuemmerle-Deschner JB, et al. Two-year results from an open-label, multicentre, phase III study evaluating the safety and efficacy of canakinumab in patients with cryopyrin-associated periodic syndrome across different severity phenotypes. Ann Rheum Dis. 2011;70(12):2095-2102.
101. Lachmann HJ, et al. Use of canakinumab in the cryopyrin-associated periodic syndrome. N Engl J Med. 2009;360(23):2416-2425.
102. Schlesinger N, et al. Canakinumab for acute gouty arthritis in patients with limited treatment options: results from two randomised, multicentre, active-controlled, double-blind trials and their initial extensions. Ann Rheum Dis. 2012;71(11):1839-1848.
103. Moran A, et al. Interleukin-1 antagonism in type 1 diabetes of recent onset: two multicentre, randomised, double-blind, placebo-controlled trials. Lancet. 2013;381(9881):1905-1915.
104. Ridker PM, et al. Effects of interleukin-1beta inhibition with canakinumab on hemoglobin A1c, lipids, C-reactive protein, interleukin-6, and fibrinogen: a phase IIb randomized, placebo-controlled trial. Circulation. 2012;126(23):2739-2748.
105. Hensen J, Howard CP, Walter V, Thuren T. Impact of interleukin-1beta antibody (canakinumab) on glycaemic indicators in patients with type 2 diabetes mellitus: results of secondary endpoints from a randomized, placebo-controlled trial. Diabetes Metab. 2013;39(6):524-531.
106. Alten R, et al. 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.
107. Ruperto N, et al. Two randomized trials of canakinumab in systemic juvenile idiopathic arthritis. N Engl J Med. 2012;367(25):2396-2406.
108. de Koning HD, Schalkwijk J, van der Ven-Jongekrijg J, Stoffels M, van der Meer JW, Simon A. Sustained efficacy of the monoclonal antiinterleukin-1 beta antibody canakinumab in a 9-month trial in Schnitzler's syndrome. Ann Rheum Dis. 2013;72(10):1634-1638.
109. Ugurlu S, Ucar D, Seyahi E, Hatemi G, Yurdakul S. Canakinumab in a patient with juvenile Behcet's syndrome with refractory eye disease. Ann Rheum Dis. 2012;71(9):1589-1591.
110. Issafras H, Corbin JA, Goldfine ID, Roell MK. Detailed mechanistic analysis of gevokizumab, an allosteric anti-IL-1β antibody with differential receptor-modulating properties. J Pharmacol Exp Ther. 2014;348(1):202-215.
111. Roell MK, et al. Kinetic approach to pathway attenuation using XOMA 052, a regulatory therapeutic antibody that modulates interleukin-1beta activity. J Biol Chem. 2010;285(27):20607-20614.
112. Cavelti-Weder C, et al. Inhibition of IL-1β improves fatigue in type 2 diabetes. Diabetes Care. 2011;34(10):e158.
113. Gul A, et al. Interleukin-1β-regulating antibody XOMA 052 (gevokizumab) in the treatment of acute exacerbations of resistant uveitis of Behcet's disease: an open-label pilot study. Ann Rheum Dis. 2012;71(4):563-566.