Low-dose interleukin 2 in patients with type 1 diabetes: A phase 1/2 randomised, double-blind, placebo-controlled trial

The Lancet Diabetes and Endocrinology

Volumn 1, Issue 4, 2013, Pages 295-305

  Hartemann, Agnès ^a   Bensimon, Gilbert ^a,c   Payan, Christine A ^a   Jacqueminet, Sophie ^a   Bourron, Olivier ^a   Nicolas, Nathalie ^a   Fonfrede, Michèle ^a   Rosenzwajg, Michelle ^b,d,e   Bernard, Claude ^b,d,e   Klatzmann, David ^b,d,e  

^a PITIÉ SALPÊTRIÈRE HOSPITAL   (France)

^b ASSISTANCE PUBLIQUE HÔPITAUX DE PARIS   (France)

^c Pharmacologie   (France)

^d Unit of Dermatology   (France)

^e CNRS   (France)

Author keywords

[No Author keywords available]

Indexed keywords

AUTOANTIBODY; C PEPTIDE; GLUCOSE; HEMOGLOBIN A1C; INSULIN; INTERLEUKIN 2; INTERLEUKIN 2 RECEPTOR; PLACEBO;

ABDOMINAL PAIN; ADULT; AGED; ALLERGIC RHINITIS; AREA UNDER THE CURVE; ARTICLE; ASTHENIA; CD4+ T LYMPHOCYTE; CHEST TIGHTNESS; CLINICAL ARTICLE; CONTROLLED STUDY; DIARRHEA; DISEASE ASSOCIATION; DISEASE EXACERBATION; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; DRUG SAFETY; DRUG TOLERANCE; DRUG USE; DYSPNEA; EFFECTOR CELL; FATIGUE; FEMALE; FLOW CYTOMETRY; FLU LIKE SYNDROME; FOLLOW UP; GLUCOSE BLOOD LEVEL; GLUCOSE METABOLISM; HEADACHE; HEMOGLOBIN BLOOD LEVEL; HUMAN; HYPERGLYCEMIA; IMMUNOTHERAPY; INJECTION SITE REACTION; INSULIN DEPENDENT DIABETES MELLITUS; INSULIN TREATMENT; LOW DRUG DOSE; LYMPHOCYTE ACTIVATION; LYMPHOCYTE COUNT; MALE; MIGRAINE; MYALGIA; NAUSEA; PHASE 1 CLINICAL TRIAL; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; RANDOMIZED CONTROLLED TRIAL; RASH; REGULATORY T LYMPHOCYTE; SIDE EFFECT; THROAT TIGHTNESS; THYROTROPIN BLOOD LEVEL; TREATMENT DURATION; TREATMENT OUTCOME; CLINICAL TRIAL; DIABETES MELLITUS, TYPE 1; DRUG EFFECTS; IMMUNOLOGY; MIDDLE AGED; YOUNG ADULT;

ADULT; DIABETES MELLITUS, TYPE 1; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; FEMALE; HUMANS; INTERLEUKIN-2; MALE; MIDDLE AGED; T-LYMPHOCYTES, REGULATORY; YOUNG ADULT;

EID: 84887625676     PISSN: 22138587     EISSN: None     Source Type: Journal    
DOI: 10.1016/S2213-8587(13)70113-X     Document Type: Article

References (30)

1. Staeva TP, Chatenoud L, Insel R, Atkinson MA Recent lessons learned from prevention and recent-onset type 1 diabetes immunotherapy trials. Diabetes 2013, 62:9-17.
2. Michels AW, Eisenbarth GS Immune intervention in type 1 diabetes. Semin Immunol 2011, 23:214-219.
3. Brunkow ME, Jeffery EW, Hjerrild KA, et al. Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse. Nat Genet 2001, 27:68-73.
4. Wing K, Sakaguchi S Regulatory T cells exert checks and balances on self tolerance and autoimmunity. Nat Immunol 2010, 11:7-13.
5. Brusko TM, Putnam AL, Bluestone JA Human regulatory T cells: role in autoimmune disease and therapeutic opportunities. Immunol Rev 2008, 223:371-390.
6. Grinberg-Bleyer Y, Baeyens A, You S, et al. IL-2 reverses established type 1 diabetes in NOD mice by a local effect on pancreatic regulatory T cells. J Exp Med 2010, 207:1871-1878.
7. Marek-Trzonkowska N, Mysliwiec M, Dobyszuk A, et al. Administration of CD4+CD25highCD127- regulatory T cells preserves beta-cell function in type 1 diabetes in children. Diabetes Care 2012, 35:1817-1820.
8. Putnam AL, Brusko TM, Lee MR, et al. Expansion of human regulatory T-cells from patients with type 1 diabetes. Diabetes 2009, 58:652-662.
9. Saadoun D, Rosenzwajg M, Joly F, et al. Regulatory T-cell responses to low-dose interleukin-2 in HCV-induced vasculitis. N Engl J Med 2011, 365:2067-2077.
10. Koreth J, Matsuoka K, Kim HT, et al. Interleukin-2 and regulatory T cells in graft-versus-host disease. N Engl J Med 2011, 365:2055-2066.
11. Wang J, Wicker LS, Santamaria P IL-2 and its high-affinity receptor: genetic control of immunoregulation and autoimmunity. Semin Immunol 2009, 21:363-371.
12. Tang Q, Adams JY, Penaranda C, et al. Central role of defective interleukin-2 production in the triggering of islet autoimmune destruction. Immunity 2008, 28:687-697.
13. Buckner JH Mechanisms of impaired regulation by CD4(+)CD25(+)FOXP3(+) regulatory T cells in human autoimmune diseases. Nat Rev Immunol 2010, 10:849-859.
14. Hulme MA, Wasserfall CH, Atkinson MA, Brusko TM Central role for interleukin-2 in type 1 diabetes. Diabetes 2012, 61:14-22.
15. Pugliese A The multiple origins of type 1 diabetes. Diabet Med 2013, 30:135-146.
16. Mallone R, Martinuzzi E, Blancou P, et al. CD8+ T-cell responses identify beta-cell autoimmunity in human type 1 diabetes. Diabetes 2007, 56:613-621.
17. Tang Q, Henriksen KJ, Bi M, et al. In vitro-expanded antigen-specific regulatory T cells suppress autoimmune diabetes. J Exp Med 2004, 199:1455-1465.
18. Long SA, Rieck M, Sanda S, et al. Rapamycin/IL-2 combination therapy in patients with type 1 diabetes augments Tregs yet transiently impairs beta-cell function. Diabetes 2012, 61:2340-2348.
19. Baeyens A, Perol L, Fourcade G, et al. Limitations of IL-2 and rapamycin in immunotherapy of type 1 diabetes. Diabetes 2013, 62:3120-3131.
20. Vial T, Descotes J Clinical toxicity of interleukin-2. Drug safety 1992, 7:417-433.
21. Sundin DJ, Wolin MJ Toxicity management in patients receiving low-dose aldesleukin therapy. Ann Pharmacother 1998, 32:1344-1352.
22. Moran A, Bundy B, Becker DJ, et al. Interleukin-1 antagonism in type 1 diabetes of recent onset: two multicentre, randomised, double-blind, placebo-controlled trials. Lancet 2013, 381:1905-1915.
23. Sherry N, Hagopian W, Ludvigsson J, et al. Teplizumab for treatment of type 1 diabetes (Protege study): 1-year results from a randomised, placebo-controlled trial. Lancet 2011, 378:487-497.
24. Holl RW, Bohm B, Loos U, Grabert M, Heinze E, Homoki J Thyroid autoimmunity in children and adolescents with type 1 diabetes mellitus. Effect of age, gender and HLA type. Horm Res 1999, 52:113-118.
25. Valle A, Jofra T, Stabilini A, Atkinson M, Roncarolo MG, Battaglia M Rapamycin prevents and breaks the anti-CD3-induced tolerance in NOD mice. Diabetes 2009, 58:875-881.
26. Yang SB, Lee HY, Young DM, et al. Rapamycin induces glucose intolerance in mice by reducing islet mass, insulin content, and insulin sensitivity. J Mol Med (Berl) 2012, 90:575-585.
27. Tanemura M, Ohmura Y, Deguchi T, et al. Rapamycin causes upregulation of autophagy and impairs islets function noth in vitro and in vivo. Am J Transplant 2012, 12:102-114.
28. Boyman O, Sprent J The role of interleukin-2 during homeostasis and activation of the immune system. Nat Rev Immunol 2012, 12:180-190.
29. Marino E, Silveira PA, Stolp J, Grey ST β cell-directed therapies in type 1 diabetes. Trends Immunol 2011, 32:287294.
30. Lysy PA, Weir GC, Bonner-Weir S Concise review: pancreas regeneration: recent advances and perspectives. Stem Cells Transl Med 2012, 1:150-159.