Interleukin-1 antagonists for diabetes

Expert Opinion on Investigational Drugs

Volumn 22, Issue 8, 2013, Pages 965-979

  Mandrup Poulsen, Thomas ^a,b  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

^b KAROLINSKA UNIVERSITY HOSPITAL   (Sweden)

Author keywords

Adaptive immunity; Autoimmunity; Autoinflammation; Beta cells; Cytokines; Inflammation; Innate immunity; Insulin resistance; Metabolism; Obesity

Indexed keywords

CANAKINUMAB; CYTOKINE; GEVOKIZUMAB; INFLAMMASOME; INSULIN; INTERLEUKIN 1; INTERLEUKIN 1 ANTIBODY; INTERLEUKIN 1 RECEPTOR BLOCKING AGENT; INTERLEUKIN 1BETA ANTIBODY; INTERLEUKIN RECEPTOR; LIGAND; METFORMIN; MONOCLONAL ANTIBODY CD3; ORAL ANTIDIABETIC AGENT; RECOMBINANT INTERLEUKIN 1 RECEPTOR BLOCKING AGENT; RILONACEPT;

ARTERY OCCLUSION; ATHEROSCLEROSIS; BRAIN EDEMA; CELL DESTRUCTION; CEREBROVASCULAR ACCIDENT; CHRONIC INFLAMMATION; DEHYDRATION; DIABETES MELLITUS; DIABETIC KETOACIDOSIS; DIABETIC NEPHROPATHY; DIABETIC RETINOPATHY; ELECTROLYTE DISTURBANCE; FOOT ULCER; GAIN OF FUNCTION MUTATION; HEART INFARCTION; HUMAN; INJECTION SITE REACTION; INSULIN DEFICIENCY; INSULIN DEPENDENT DIABETES MELLITUS; INSULIN RELEASE; INSULIN RESISTANCE; INSULIN SENSITIVITY; INTRACELLULAR SIGNALING; LIPOTOXICITY; LUNG EDEMA; MORBIDITY; MORTALITY; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; NONKETOTIC DIABETIC COMA; OBESITY; PANCREAS ISLET BETA CELL; PERIPHERAL NEUROPATHY; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PROTEIN EXPRESSION; REVIEW;

ANIMALS; DIABETES MELLITUS, TYPE 1; DIABETES MELLITUS, TYPE 2; HUMANS; HYPOGLYCEMIC AGENTS; INTERLEUKIN-1;

EID: 84880229974     PISSN: 13543784     EISSN: 17447658     Source Type: Journal    
DOI: 10.1517/13543784.2013.804060     Document Type: Review

References (105)

1. IDF Diabetes Atlas 5th Edition, 2012 Update. The global Burden. International Diabetes Federation. Available from: Http://www.idf.org/ diabetesatlas/5e/the-global-burden [Last accessed 18 January 2013]
2. Caballero B. The global epidemic of obesity: An overview. Epidemiol Rev 2007;29:1-5
3. Gershell L. Type 2 diabetes market. Nat Rev Drug Dis 2005;4:367-8
4. Hauber A, Gale EAM. The market in diabetes. Diabetologia 2006;49:247-52
5. Transparency Market Research. Global diabetes devices market and diabetes drugs market - industry scenario, trends, analysis, size, share & forecast 2011 - 2018. 2012. Available from: Http://www.transparencymarketresearch. com [Last accessed 18 January 2013]
6. Dinarello CA. Interleukin-1 in the pathogenesis and treatment of inflammatory diseases. Blood 2011;117:3720-32
7. Yoon D-Y, Dinarello CA. Differential effects of anti-IL-1R accessory protein antibodies on IL-1a or IL-1b induced production of PGE2 or IL-6 from 3T3 L1 cells. J Biochem Mol Biol 2007;40:562-70
8. Bendtzen K, Mandrup-Poulsen T, Nerup J, et al. Cytotoxicity of human pI 7 interleukin 1 for pancreatic islets of Langerhans. Science 1986;232:1545-7
9. Zumsteg U, Reimers JI, Pociot F, et al. Differential IL-1 receptor antagonism on rodent and human pancreatic islet - and a cells. Diabetologia 1993;36:759-66
10. Talukdar S, Oh DY, Bandyopadhyay G, et al. Neutrophils mediate insulin resistance in mice fed a high-fat diet through secreted elastase. Nat Med 2012;18:1407-12
11. Ehses JA, Perren A, Eppler E, et al. Increased number of islet-associated macrophages in type 2 diabetes. Diabetes 2007;56:2356-70
12. Martinon F, Mayor A, Tschopp J. The inflammasomes: Guardians of the body. Annu Rev Immunol 2009;27:229-65
13. Zhou R, Tardivel A, Thorens B, et al. Thioredoxin-interacting protein links oxidative stress to inflammasome activation. Nat Immunol 2010;11:136-40
14. Masters SL, Dunne A, Subramanian SL, et al. Activation of the NLRP3 inflammasome by islet amyloid polypeptide provides a mechanism for enhanced IL-1b in type 2 diabetes. Nat Immunol 2010;11:897-904
15. Westwell-Roper C, Dai DL, Soukhatcheva G, et al. IL-1 blockade attenuates islet amyloid polypeptide-induced proinflammatory cytokine release and pancreatic islet graft dysfunction. J Immunol 2011;187:2755-65
16. Menu P, Mayor A, Zhou R, et al. ER stress activates the NLRP3 inflammasome via an UPR-independent pathway. Cell Death Dis 2012;3:e261
17. Lerner AG, Upton JP, Praveen PV, et al. IRE1a induces thioredoxin-interacting protein to activate the NLRP3 inflammasome and promote programmed cell death under irremediable ER stress. Cell Metab 2012;16:250-64
18. Oslowski CM, Hara T, O'Sullivan-Murphy B, et al. Thioredoxin-interacting protein mediates ER stress-induced b cell death through initiation of the inflammasome. Cell Metab 2012;16:265-73
19. Wen H, Ting JPY, O'Neill LAJ. A role for the NLRP3 inflammasome in metabolic diseases-did Warburg miss inflammatioñ Nat Immunol 2012;13:352-7
20. van de Veerdonk FL, Smeekens SP, Joosten LA, et al. Reactive oxygen species-independent activation of the IL-1beta inflammasome in cells from patients with chronic granulomatous disease. Proc Natl Acad Sci USA 2010;107:3030-3
21. Subramanian N, Natarajan K, Clatworthy MR, et al. The adaptor MAVAS promotes NLRP3 mitochondrial localization and inflammasome activation. Cell 2013;153:348-61
22. Wang Y, Yang C, Mao K, et al. Cellular localization of NLRP3 inflammasome. Protein Cell 2013; Epub ahead of print
23. Dinarello CA. Immunological and inflammatory functions of the interleukin-1 family. Ann Rev Immunol 2009;27:519-50
24. van de Veerdonk FL, Stoeckman AK, Wu G, et al. IL-38 binds to the IL-36 receptor and has biological effects on immune cells similar to IL-36 receptor antagonist. PNAS 2012;109:3001-5
25. Tortola L, Rosenwald E, Abel B, et al. Psoriasiform dermatitis is driven by IL-36-mediated DC-keratinocyte crosstalk. J Clin Invest 2012;122:3965-76
26. Lee JK, Kim SH, Lewis EC, et al. Differences in signaling pathways by IL-1b and IL-18. Proc Natl Acad Sci USA 2004;101:8815-20
27. Kunikata T, Torigoe K, Ushio S, et al. Constitutive and induced IL-18 receptor expression by various peripheral blood cell subsets as determined by anti-hIL-18r monoclonal antibody. Cell Immunol 1998;189:135-43
28. Chackerian AA, Oldham ER, Murphy EE, et al. IL-1 receptor accessory protein and ST2 comprise the IL-33 receptor complex. J Immunol 2007;179:2551-5
29. Dinarello CA. The many worlds of reducing interleukin-1. Arthritis Rheum 2005;52:1960-7 Available from http://www.prnewswire. com/news-releases/twi- pharmaceuticalsannounces-positive-phase-iib-clinical-trialresults-of-ac-201-in- patients-with-type-2-diabetes-165107926.html
30. Akeson CAL, Woods CW, Hsieh LC, et al. AF12198, a novel low molecular weight antagonist, selectively binds the human type I Interleukin (IL)-1 receptor and blocks in vivo responses to IL-1. J Biol Chem 1996;271:30517-23
31. Sarabu R, Cooper JP, Cook CM, et al. Design and synthesis of small molecule interleukin-1 receptor antagonists based on a benzene template. Drug Des Discov 1998;15:191-8
32. Quiniou C, Sapieha P, Lahaie I, et al. Development of a novel noncompetitive antagonist of IL-1 receptor. J Immunol 2008;180:6977-87
33. Kastner DL, Aksentijevich I, Goldbach-Mansky R. Autoinflammatory disease re-loaded: A clinical perspective. Cell 2010;140:784-90
34. Savic S, Dickie LJ, Wittmann M, McDermott MF. Autoinflammatory syndromes and cellular responses to stress: Pathophysiology, diagnosis and new treatment perspectives. Best Pract Res Clin Rheumatol 2012;26:505-33
35. Dinarello CA, Simon A, van der Meer JWM. Treating inflammation by blocking interleukin-1 in a broad spectrum of diseases. Nat Rev Drug Dis 2012;11:633-52
36. Aaltonen KJ, Virkki LM, Malmivaara A, et al. Systematic review and meta-analysis of the efficacy and safety of existing TNF blocking agents in treatment of rheumatoid arthritis. PLoS One 2012;7:e30275
37. WHO. Definition, diagnosis and classification of diabetes mellitus and its complications. Report of a consultation, Part 1: Diagnosis and classification of diabetes mellitus. World Health Organisation, Geneva; 1999. WHO/NCD/NCS/99.2
38. Fourlanos S, Narendran P, Byrnes GB, et al. Insulin resistance is a risk factor for progression to type 1 diabetes. Diabetologia 2004;47:1661-7
39. Halban PA, Hitchins S, Koivisto VA, et al. DIAMAP. Road map for diabetes research in Europe. Road map report. Strategic plan for diabetes research. 2010.p. 1-199. Available from: Www. DIAMAP.eu
40. Billings LK, Florez JC. The genetics of type 2 diabetes: What have we learned from GWAS? Ann NY Acad Sci 2010;1212:59-77
41. Hansen JB, Tonnesen MF, Madsen AN, et al. Divalent metal transporter 1 regulates iron-mediated ROS and pancreatic beta-cell fate in response to cytokines. Cell Metab 2012;16:1-13
42. Zhang X, Zhang G, Zhang H, et al. Hypothalamic IKKb/NF-kB and ER stress link overnutrition to energy imbalance and obesity. Cell 2008;135:61-73
43. Konner AC, Brüning JC. Selective insulin and leptin resistance in metabolic disorders. Cell Metab 2012;16:144-52
44. Meng Q, Cai D. Defective hypothalamic autophagy directs the central pathogenesis of obesity via the IkB kinase b (IKKb)/NF-kB pathway. J Biol Chem 2011;286:32324-32
45. Hotamisligil GS, Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor-alpha: Direct role in obesity-linked insulin resistance. Science 1993;259:87-91
46. Rutkowski JM, Davis KE, Scherer PE. Mechanisms of obesity and related pathologies: The macro- and microcirculation of adipose tissue. FEBS J 2009;276:5738-46
47. Ueki K, Kondo T, Kahn CR. Suppressor of cytokine signalling 1 (SOCS-1) and SOCS-3 cause insulin resistance through inhibition of tyrosine phosphorylation of insulin receptor substrate proteins by discrete mechanisms. Mol Cell Biol 2004;24:5434-46
48. Rui L, Yuan M, Frantz D, et al. SOCS-1 and SOCS-3 block insulin signaling by ubiquitin-mediated degradation of IRS1 and IRS2. J Biol Chem 2002;277:42394-8
49. Tack CJ, Stienstra R, Joosten LA, Netea MG. Inflammation links excess fat to insulin resistance: The role of the interleukin-1 family. Immunol Rev 2012;249:239-52
50. Mathis D, Vence L, Benoist C. b-Cell death during progression to diabetes. Nature 2001;414:792-8
51. van Belle TL, Coppieters KT, von Herrath MG. Type 1 diabetes: Etiology, immunology, and therapeutic strategies. Physiol Rev 2011;91:79-118
52. Donath MY, Størling J, Berchtold LA, et al. Cytokines and beta-cell biology: From concept to clinical translation. Endocr Rev 2008;29:334-50
53. Mandrup-Poulsen T, Bendtzen K, Nerup J, et al. Affinity purified human interleukin I is cytotoxic to isolated islets of Langerhans. Diabetologia 1986;29:63-7
54. Mandrup-Poulsen T. The role of interleukin-1 in the pathogenesis of IDDM. Diabetologia 1996;39:1005-29
55. Eizirik DL, Mandrup-Poulsen T. A choice of death - the signal-transduction of immune-mediated beta cell apoptosis. Diabetologia 2001;44:2115-33
56. Mandrup-Poulsen T, Pickersgill LMS, Donath MY. Blockade of Interleukin 1 in type 1 diabetes mellitus. Nat Rev Endocrinol 2010;6:158-66
57. Pfleger C, Mortensen HB, Hansen L, Hvidøre Study Group on Childhood Diabetes. Association of IL-1ra and adiponectin with C-peptide and remission in patients with type 1 diabetes. Diabetes 2008;57:929-37
58. Thomas HE, Irawaty W, Darwiche R, et al. IL-1 receptor deficiency slows progression to diabetes in the NOD mouse. Diabetes 2004;53:113-21
59. Ablamunits V, Henegariu O, Hansen JB, et al. Synergistic reversal of type 1 diabetes in NOD mice with anti-adaptive and innate immune modulators Diabetes. 2012;61:145-54
60. Sandberg JO, Eizirik DL, Sandler S. IL-1 receptor antagonist inhibits recurrence of disease after syngeneic pancreatic islet transplantation to spontaneously diabetic non-obese diabetic (NOD) mice. Clin Exp Immunol 1997;108:314-17
61. Evans JL, Goldfine ID, Maddux BA, et al. Are oxidative-stress activated signalling pathways mediators of insulin resistance and beta-cell dysfunctioñ Diabetes 2003;52:1-8
62. Dinarello CA, Donath MY, Mandrup-Poulsen T. Role of IL-1b in type 2 diabetes. Curr Opinion Endocrinol Diab Obesity 2010;17:314-21
63. Donath MY, Shoelson SE. Type 2 diabetes as an inflammatory disease. Nat Rev Immunol 2011;11:98-107
64. Maedler K, Sergeev P, Jan A, et al. Leptin modulates b-cell expression of IL-1 receptor antagonist and release of IL-1b in human islets. Proc Natl Acad Sci USA 2004;101:8138-43
65. Maedler K, Sergeev P, Ris F, et al. Glucose-induced beta cell production of IL-1beta contributes to glucotoxicity in human pancreatic islets. J Clin Invest 2002;110:851-60
66. Ehses JA, Lacraz G, Giroix MH, et al. IL-1 antagonism reduces hyperglycemia and tissue inflammation in the type 2 diabetic GK rat. Proc Natl Acad Sci USA 2009;106:13998-4003
67. Akash MS, Rehman K, Sun H, Chen S. Sustained delivery of IL-1Ra from PF127-gel reduces hyperglycemia in diabetic GK-rats. PLoS ONE 2013;8(2):e55925
68. Akash MS, Rehman K, Sun H, Chen S. Interleukin-1 receptor antagonist improves normoglycemia and insulin sensitivity in diabetic Goto-Kakizaki-rats. Eur J Pharmacol 2013;701:87-95
69. Blamire AM, Anthony DC, Rajagopalan B, et al. Interleukin-1beta -induced changes in blood-brain barrier permeability, apparent diffusion coefficient, and cerebral blood volume in the rat brain: A magnetic resonance study. J Neurosci 2000;20:8153-9
70. Glaser N. Cerebral injury and cerebral edema in children with diabetic ketoacidosis: Could cerebral ischemia and reperfusion injury be involved? Pediatr Diabetes 2009;10:534-41
71. Dalton RR, Hoffman WH, Passmore GG, Martin SL. Plasma C-reactive protein levels in severe diabetic ketoacidosis. Ann Clin Lab Sci 2003;33:435-42
72. Hoffman WH, Burek CL, Waller JL, et al. Cytokine response to diabetic ketoacidosis and its treatment. Clin Immunol 2003;108:175-81 Available from: Http://clinicaltrials.gov/ct2/show/NCT01477476
73. Gogos CA, Giali S, Paliogianni F, et al. Interleukin-6 and C-reactive protein as early markers of sepsis in patients with diabetic ketoacidosis or hyperosmosis. Diabetologia 2001;44:1011-14
74. Du M, Basu A, Fu D, et al. Serum inflammatory markers and preeclampsia in type 1 diabetes: A prospective study. Diabetes Care 2013; Epub ahead of print
75. del Rey A, Roggero E, Randolf A, et al. IL-1 resets glucose homeostasis at central levels. Proc Natl Acad Sci USA 2006;103:16039-44
76. Dotson S, Freeman R, Failing HJ, Adler GK. Hypoglycemia increases serum interleukin-6 levels in healthy men and women. Diabetes Care 2008;31:1222-3
77. Masters SL, Latz E, O'Neill LA. The inflammasome in atherosclerosis and type 2 diabetes. Sci Transl Med 2011;3:81ps17
78. Duewell P, Kono H, Rayner KJ, et al. NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals. Nature 2010;464:1357-61
79. Menu P, Pellegrin M, J-F Aubert JF, et al. Atherosclerosis in ApoE-deficient mice progresses independently of the NLRP3 inflammasome. Cell Death Dis 2011;2:e137
80. Isoda K, Sawada S, Ishigami N, et al. Lack of interleukin-1 receptor antagonist modulates plaque composition in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 2004;24:1068-73
81. Marculescu R, Endler G, Schillinger M, et al. Interleukin-1 receptor antagonist genotype is associated with coronary atherosclerosis in patients with type 2 diabetes. Diabetes 2002;51:3582-5
82. Vincent JA, Mohr S. Inhibition of caspase-1/interleukin-1b signaling prevents degeneration of retinal capillaries in diabetes and galactosemia. Diabetes 2007;56:224-30
83. Trueblood KE, Mohr S, Dubyak GR. Purinergic regulation of high-glucose-induced caspase-1 activation in the rat retinal Müller cell line rMC-1. Am J Physiol Cell Physiol 2011;301:C1213-23
84. Gong W, Liu ZH, Zeng CH, et al. Amylin deposition in the kidney of patients with diabetic nephropathy. Kidney Int 2007;72:213-18
85. Vilaysane A, Chun J, Seamone ME, et al. The NLRP3 inflammasome promotes renal inflammation and contributes to CKD. J Am Soc Nephrol 2010;21:1732-44
86. Satirapoj B. Review on pathophysiology and treatment of diabetic kidney disease. J Med Assoc Thai 2010;93(Suppl 6):S228-41
87. Sumpter KM, Adhikari S, Grishman EK, et al. Preliminary studies related to anti-interleukin-1b therapy in children with newly diagnosed type 1 diabetes. Pediatr Diabetes 2011;12:656-67
88. Moran A, Bundy B, Becker DJ, et al. Interleukin-1 antagonism in type 1 diabetes of recent onset: Two multicenter, randomized double-masked, placebo-controlled trials. Lancet 2013;In press . First randomized, placebo-controlled trials in recent-onset type 1 diabetes.
89. Shah SC, Malone JI, Simpson NE. A randomized trial of intensive insulin therapy in newly diagnosed insulin-dependent diabetes mellitus. N Engl J Med 1989;320:550-4
90. van Asseldonk EJP, van Poppel PC, Ballak DB, et al. One week of treatment with the IL-1 receptor antagonist anakinra improves insulin sensitivity in patients with type 1 diabetes mellitus: Results from a clinical trial. Diabetologia 2012;55(Suppl 1):A560
91. Larsen CM, Faulenbach M, Vaag A, et al. Interleukin-1 receptor antagonist in type 2 diabetes mellitus. N Engl J Med 2007;356:1517-26
92. Larsen CM, Faulenbach M, Vaag A, et al. Sustained effect of interleukin-1-receptor antagonist treatment on beta-cell function in type 2 diabetes mellitus. Diabetes Care 2009;32:1663-8
93. Cavelti-Weder C, Babiens-Brunner A, Keller C, et al. Ef6fects of gevokizumab on glycemia and inflammatory markers in type 2 diabetes. Diabetes Care 2012;35:1654-62
94. XOMA. XOMA 052 Phase 2b Top Line Results: Glucose Control Not Demonstrated, Positive Anti-inflammatory Effect, Cardiovascular Biomarker and Lipid Improvement and Safety Confirmed. 2011. Available from: Http://investors.xoma.com/releasedetail. cfm?ReleaseID=559470
95. Rissanen A, Howard CP, Botha J, et al. Effect of anti-IL-1b antibody (canakinumab) on insulin secretion rates in impaired glucose tolerance or type 2 diabetes: Results of a randomized, placebo-controlled trial. Diab Obes Metab 2012;14:1088-96
96. Ridker PM, Campbell P, Howard CP, et al. Effects of interleukin-1b inhibition with Canakinumab on hemoglobin A1c, lipids, C-reactive protein, interleukin-6, and fibrinogen. A phase IIb randomized, placebo-controlled trial. Circulation 2012;126:2739-48
97. Sloan-Lancaster J, Abu-Raddad E, Polzer J, et al. Safety, tolerability and efficacy of subcutaneous (SC) LY2189102, a neutralising IL-1b antibody, in patients (Pts) with type 2 diabetes. Diabetologia 2011;54(Suppl1):A898
98. van Asseldonk EJ, Stienstra R, Koenen TB, et al. Treatment with anakinra improves disposition index but not insulin sensitivity in nondiabetic subjects with the metabolic syndrome: A randomized, double-blind, placebo-controlled study. J Clin Endocrinol Metab 2011;96:2119-26
99. The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study Research Group. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med 2005;353:2643-53
100. Holman RR, Paul SK, Bethel MA, et al. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 2008;359:1577-89
101. Mandrup-Poulsen T. Perspective: Testing failures. Nature 2012;485:S17
102. Greenbaum CJ, Mandrup-Poulsen T, Battelino T, et al. Randomized comparisons of the mixed meal tolerance test versus the glucagon stimulation test for the assessment of beta cell function in type 1 diabetes. Diabetes Care 2008;31:1966-71
103. García MC, Wernstedt I, Berndtsson A, et al. Mature-onset obesity in interleukin-1 receptor i knockout mice diabetes. 2006;55:1205-13
104. Hirsch E, Irikura VM, Paul SM, Hirsh D. Functions of interleukin 1 receptor antagonist in gene knockout and overproducing mice. Proc Natl Acad Sci USA 1996;93:11008-13
105. Matsuki T, Horai R, Sudo K, Iwakura Y. IL-1 plays an important role in lipid metabolism by regulating insulin levels under physiological conditions. J Exp Med 2003;198:877-88