Vaccination with IL-6 analogues induces autoantibodies to IL-6 and influences experimentally induced inflammation

International Immunopharmacology

Volumn 7, Issue 13, 2007, Pages 1704-1713

  Galle, Pia ^a   Jensen, Lene ^b   Andersson, Christina ^b   Cuzzocrea, Salvatore ^c   Di Paola, Rosanna ^c   Nicoletti, Ferdinando ^a,d   Svenson, Morten ^a   Bendtzen, Klaus ^a   Thomsen, Allan R ^e   Hansen, Morten B ^a  

^a Rigshospitalet   (Denmark)

^b LEO PHARMA A S   (Denmark)

^c UNIVERSITY OF MESSINA   (Italy)

^d UNIVERSITY OF CATANIA   (Italy)

^e UNIVERSITY OF COPENHAGEN   (Denmark)

Author keywords

Antibodies; Cytokines; Endotoxin shock; Inflammation; Vaccination

Indexed keywords

AUTOANTIBODY; COLLAGEN; INTERLEUKIN 6; INTERLEUKIN 6 ANTIBODY; LIPOPOLYSACCHARIDE; TUMOR NECROSIS FACTOR ALPHA;

ALLERGIC ENCEPHALITIS; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTHRITIS; ARTICLE; CONTROLLED STUDY; IMMUNOCOMPETENCE; IMMUNOTHERAPY; INFLAMMATION; MOUSE; MOUSE STRAIN; NONHUMAN; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; VACCINATION;

ANIMALS; ARTHRITIS, EXPERIMENTAL; AUTOANTIBODIES; ENCEPHALOMYELITIS, AUTOIMMUNE, EXPERIMENTAL; INTERLEUKIN-6; LIPOPOLYSACCHARIDES; MICE; MICE, INBRED STRAINS; SERUM AMYLOID A PROTEIN; TUMOR NECROSIS FACTOR-ALPHA; VACCINATION;

EID: 35748943527     PISSN: 15675769     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.intimp.2007.08.026     Document Type: Article

References (71)

1. Ross C., Svenson M., Hansen M.B., Vejlsgaard G.L., and Bendtzen K. High avidity IFN-neutralizing antibodies in pharmaceutically prepared human IgG. J Clin Invest 95 (1995) 1974-1978
2. Svenson M., Hansen M.B., and Bendtzen K. Binding of cytokines to pharmaceutically prepared human immunoglobulin. J Clin Invest 92 (1993) 2533-2539
3. Svenson M., Hansen M.B., Ross C., Diamant M., Rieneck K., and Nielsen H. Antibody to granulocyte-macrophage colony-stimulating factor is a dominant anti-cytokine activity in human IgG preparations. Blood 91 (1998) 2054-2061
4. Hansen M.B., Svenson M., and Bendtzen K. Serum-induced suppression of interferon (IFN) activity. Lack of evidence for the presence of specific autoantibodies to IFN-alpha in normal human sera. Clin Exp Immunol 88 (1992) 559-562
5. Hansen M.B., Svenson M., Diamant M., and Bendtzen K. High-affinity IgG autoantibodies to IL-6 in sera of normal individuals are competitive inhibitors of IL-6 in vitro. Cytokine 5 (1993) 72-80
6. Hansen M.B., Svenson M., Abell K., Varming K., Nielsen H.P., and Bertelsen A. Sex- and age-dependency of IgG auto-antibodies against IL-1 alpha in healthy humans. Eur J Clin Invest 24 (1994) 212-218
7. Galle P., Svenson M., Bendtzen K., and Hansen M.B. High levels of neutralizing IL-6 autoantibodies in 0.1% of apparently healthy blood donors. Eur J Immunol 34 (2004) 3267-3275
8. Hansen M.B., Svenson M., Diamant M., and Bendtzen K. Anti-interleukin-6 antibodies in normal human serum. Scand J Immunol 33 (1991) 777-781
9. Hansen M.B., Galle P., Salomo M., Svenson M., Dickmeiss E., and Gimsing P. Transfusion-related inhibition of cytokines (TRICK). Experimental transfer of neutralizing autoantibodies to interleukin-6 by plasma transfusions. Vox Sang 92 (2007) 213-223
10. Nishimoto N., and Kishimoto T. Interleukin 6: from bench to bedside. Nat Clin Pract Rheumatol 2 (2006) 619-626
11. Trikha M., Corringham R., Klein B., and Rossi J.F. Targeted anti-interleukin-6 monoclonal antibody therapy for cancer: a review of the rationale and clinical evidence. Clin Cancer Res 9 (2003) 4653-4665
12. Ciapponi L., Maione D., Scoumanne A., Costa P., Hansen M.B., Svenson M., et al. Induction of interleukin-6 (IL-6) autoantibodies through vaccination with an engineered IL-6 receptor antagonist. Nat Biotechnol 15 (1997) 997-1001
13. Galle P., Hougs L., Barington T., Svenson M., Svejgaard A., Thomsen A.R., et al. Knocking out IL-6 by vaccination. Eur J Immunol 34 (2004) 291-300
14. Smolen J.S., and Maini R.N. Interleukin-6: a new therapeutic target. Arthritis Res Ther 8 Suppl 2 (2006) S5
15. Nishimoto N., Hashimoto J., Miyasaka N., Yamamoto K., Kawai S., Takeuchi T., et al. Study of active controlled monotherapy used for rheumatoid arthritis, an IL-6 inhibitor (SAMURAI): evidence of clinical and radiographic benefit from an x ray reader-blinded randomised controlled trial of tocilizumab. Ann Rheum Dis 66 (2007) 1162-1167
16. Houssiau F.A., Devogelaer J.P., Van D.J., and de Deuxchaisnes C.N. Interleukin-6 in synovial fluid and serum of patients with rheumatoid arthritis and other inflammatory arthritides. Arthritis Rheum 31 (1988) 784-788
17. Kotake S., Sato K., Kim K.J., Takahashi N., Udagawa N., Nakamura I., et al. Interleukin-6 and soluble interleukin-6 receptors in the synovial fluids from rheumatoid arthritis patients are responsible for osteoclast-like cell formation. J Bone Miner Res 11 (1996) 88-95
18. Zwerina J., Redlich K., Schett G., and Smolen J.S. Pathogenesis of rheumatoid arthritis: targeting cytokines. Ann N Y Acad Sci 1051 (2005) 716-729
19. Nishimoto N., Yoshizaki K., Maeda K., Kuritani T., Deguchi H., Sato B., et al. Toxicity, pharmacokinetics, and dose-finding study of repetitive treatment with the humanized anti-interleukin 6 receptor antibody MRA in rheumatoid arthritis. Phase I/II clinical study. J Rheumatol 30 (2003) 1426-1435
20. Alonzi T., Fattori E., Lazzaro D., Costa P., Probert L., Kollias G., et al. Interleukin 6 is required for the development of collagen-induced arthritis. J Exp Med 187 (1998) 461-468
21. Sasai M., Saeki Y., Ohshima S., Nishioka K., Mima T., Tanaka T., et al. Delayed onset and reduced severity of collagen-induced arthritis in interleukin-6-deficient mice. Arthritis Rheum 42 (1999) 1635-1643
22. Martin R., McFarland H.F., and McFarlin D.E. Immunological aspects of demyelinating diseases. Annu Rev Immunol 10 (1992) 153-187
23. Padberg F., Feneberg W., Schmidt S., Schwarz M.J., Korschenhausen D., Greenberg B.D., et al. CSF and serum levels of soluble interleukin-6 receptors (sIL-6R and sgp130), but not of interleukin-6 are altered in multiple sclerosis. J Neuroimmunol 99 (1999) 218-223
24. Woodroofe M.N., and Cuzner M.L. Cytokine mRNA expression in inflammatory multiple sclerosis lesions: detection by non-radioactive in situ hybridization. Cytokine 5 (1993) 583-588
25. Rieckmann P., Albrecht M., Kitze B., Weber T., Tumani H., Broocks A., et al. Cytokine mRNA levels in mononuclear blood cells from patients with multiple sclerosis. Neurology 44 (1994) 1523-1526
26. Navikas V., Matusevicius D., Soderstrom M., Fredrikson S., Kivisakk P., et al. Increased interleukin-6 mRNA expression in blood and cerebrospinal fluid mononuclear cells in multiple sclerosis. J Neuroimmunol 64 (1996) 63-69
27. Eugster H.P., Frei K., Kopf M., Lassmann H., and Fontana A. IL-6-deficient mice resist myelin oligodendrocyte glycoprotein-induced autoimmune encephalomyelitis. Eur J Immunol 28 (1998) 2178-2187
28. Mendel I., Katz A., Kozak N., Ben-Nun A., and Revel M. Interleukin-6 functions in autoimmune encephalomyelitis: a study in gene-targeted mice. Eur J Immunol 28 (1998) 1727-1737
29. Okuda Y., Sakoda S., Bernard C.C., Fujimura H., Saeki Y., Kishimoto T., et al. IL-6-deficient mice are resistant to the induction of experimental autoimmune encephalomyelitis provoked by myelin oligodendrocyte glycoprotein. Int Immunol 10 (1998) 703-708
30. Samoilova E.B., Horton J.L., Hilliard B., Liu T.S., Chen Y., et al. IL-6-deficient mice are resistant to experimental autoimmune encephalomyelitis: roles of IL-6 in the activation and differentiation of autoreactive T cells. J Immunol 161 (1998) 6480-6486
31. Tilg H., Dinarello C.A., and Mier J.W. IL-6 and APPs: anti-inflammatory and immunosuppressive mediators. Immunol Today 18 (1997) 428-432
32. Kishimoto T. Interleukin-6: discovery of a pleiotropic cytokine. Arthritis Res Ther 8 Suppl 2 (2006) S2
33. Schindler R., Mancilla J., Endres S., Ghorbani R., Clark S.C., Dinarello C.A., et al. Correlations and interactions in the production of interleukin-6 (IL-6), IL-1, and tumor necrosis factor (TNF) in human blood mononuclear cells: IL-6 suppresses IL-1 and TNF. Blood 75 (1990) 40-47
34. Starkie R., Ostrowski S.R., Jauffred S., Febbraio M., and Pedersen B.K. Exercise and IL-6 infusion inhibit endotoxin-induced TNF-alpha production in humans. FASEB J 17 (2003) 884-886
35. Steensberg A., Fischer C.P., Keller C., Moller K., and Pedersen B.K. IL-6 enhances plasma IL-1ra, IL-10, and cortisol in humans. Am J Physiol Endocrinol Metab 285 (2003) E433-E437
36. Matthys P., Mitera T., Heremans H., Van Damme J., and Billiau A. Anti-gamma interferon and anti-interleukin-6 antibodies affect staphylococcal enterotoxin B-induced weight loss, hypoglycemia, and cytokine release in d-galactosamine-sensitized and unsensitized mice. Infect Immun 63 (1995) 1158-1164
37. Hansen M.B., Svenson M., Abell K., Yasukawa K., Diamant M., and Bendtzen K. Influence of interleukin-6 (IL-6) autoantibodies on IL-6 binding to cellular receptors. Eur J Immunol 25 (1995) 348-354
38. Kopf M., Baumann H., Freer G., Freudenberg M., Lamers M., Kishimoto T., et al. Impaired immune and acute-phase responses in interleukin-6-deficient mice. Nature 368 (1994) 339-342
39. Fattori E., Cappelletti M., Costa P., Sellitto C., Cantoni L., Carelli M., et al. Defective inflammatory response in interleukin 6-deficient mice. J Exp Med 180 (1994) 1243-1250
40. Ross C., Svenson M., Nielsen H., Lundsgaard C., Hansen M.B., and Bendtzen K. Increased in vivo antibody activity against interferon alpha, interleukin-1alpha, and interleukin-6 after high-dose Ig therapy. Blood 90 (1997) 2376-2380
41. Stuart J.M., Townes A.S., and Kang A.H. Collagen autoimmune arthritis. Annu Rev Immunol 2 (1984) 199-218
42. Stark J.L., and Cross A.H. Differential expression of suppressors of cytokine signaling-1 and -3 and related cytokines in central nervous system during remitting versus non-remitting forms of experimental autoimmune encephalomyelitis. Int Immunol 18 (2006) 347-353
43. Wraith D.C. Anti-cytokine vaccines and the immunotherapy of autoimmune diseases. Eur J Immunol 36 (2006) 2844-2848
44. Uyttenhove C., Arendse B., Stroobant V., Brombacher F., and van Snick J. Development of an anti-IL-12 p40 auto-vaccine: protection in experimental autoimmune encephalomyelitis at the expense of increased sensitivity to infection. Eur J Immunol 34 (2004) 3572-3581
45. Uyttenhove C., and van Snick J. Development of an anti-IL-17A auto-vaccine that prevents experimental auto-immune encephalomyelitis. Eur J Immunol 36 (2006) 2868-2874
46. Sonderegger I., Rohn T.A., Kurrer M.O., Iezzi G., Zou Y., and Kastelein R.A. Neutralization of IL-17 by active vaccination inhibits IL-23-dependent autoimmune myocarditis. Eur J Immunol 36 (2006) 2849-2856
47. Rohn T.A., Jennings G.T., Hernandez M., et al. Vaccination against IL-17 suppresses autoimmune arthritis and encephalomyelitis. Eur J Immunol 36 (2006) 2857-2867
48. Rettig M.B. Interleukin-6: an antagonizing problem becomes a solution. Nat Biotechnol 15 (1997) 952-953
49. Hertz M., Mahalingam S., Dalum I., Klysner S., Mattes J., Neisig A., et al. Active vaccination against IL-5 bypasses immunological tolerance and ameliorates experimental asthma. J Immunol 167 (2001) 3792-3799
50. Dalum I., Butler D.M., Jensen M.R., et al. Therapeutic antibodies elicited by immunization against TNF-alpha. Nat Biotechnol 17 (1999) 666-669
51. Zuany-Amorim C., Manlius C., Dalum I., Jensen M.R., Gautam A., Pay G., et al. Induction of TNF-alpha autoantibody production by AutoVac TNF106: a novel therapeutic approach for the treatment of allergic diseases. Int Arch Allergy Immunol 133 (2004) 154-163
52. Waterston A.M., Gumbrell L., Bratt T., Waller S., Gustav-Aspland J., L'hermenier C., et al. Phase I study of TNFalpha AutoVaccIne in patients with metastatic cancer. Cancer Immunol Immunother 54 (2005) 848-857
53. Capini C.J., Bertin-Maghit S.M., Bessis N., Haumont P.M., Bernier E.M., Muel E.G., et al. Active immunization against murine TNFalpha peptides in mice: generation of endogenous antibodies cross-reacting with the native cytokine and in vivo protection. Vaccine 22 (2004) 3144-3153
54. Hansen M.B., Svenson M., Diamant M., Abell K., and Bendtzen K. Interleukin-6 autoantibodies: possible biological and clinical significance. Leukemia 9 (1995) 1113-1115
55. Svenson M., Hansen M.B., Thomsen A.R., et al. Cytokine vaccination: neutralising IL-1alpha autoantibodies induced by immunisation with homologous IL-1alpha. J Immunol Methods 236 (2000) 1-8
56. Zagury D., Burny A., and Gallo R.C. Toward a new generation of vaccines: the anti-cytokine therapeutic vaccines. Proc Natl Acad Sci U S A 98 (2001) 8024-8029
57. Lu Z.Y., Brochier J., Wijdenes J., Brailly H., Bataille R., Klein B., et al. High amounts of circulating interleukin (IL)-6 in the form of monomeric immune complexes during anti-IL-6 therapy. Towards a new methodology for measuring overall cytokine production in human in vivo. Eur J Immunol 22 (1992) 2819-2824
58. Montero-Julian F.A., Gautherot E., Wijdenes J., Klein B., Brailly H., et al. Pharmacokinetics of interleukin-6 during therapy with anti-interleukin-6 monoclonal antibodies: enhanced clearance of interleukin-6 by a combination of three anti-interleukin-6 antibodies. J Interferon Res 14 (1994) 301-302
59. Presta L.G. Engineering of therapeutic antibodies to minimize immunogenicity and optimize function. Adv Drug Deliv Rev 58 (2006) 640-656
60. Aybay C., Ozel S., and Aybay C. Demonstration of specific antibodies against infliximab induced during treatment of a patient with ankylosing spondylitis. Rheumatol Int 26 (2006) 473-480
61. Bendtzen K., Geborek P., Svenson M., Larsson L., Kapetanovic M.C., and Saxne T. Individualized monitoring of drug bioavailability and immunogenicity in rheumatoid arthritis patients treated with the tumor necrosis factor alpha inhibitor infliximab. Arthritis Rheum 54 (2006) 3782-3789
62. Kopf M., Herren S., Wiles M.V., Pepys M.B., and Kosco-Vilbois M.H. Interleukin 6 influences germinal center development and antibody production via a contribution of C3 complement component. J Exp Med 188 (1998) 1895-1906
63. Ladel C.H., Blum C., Dreher A., Reifenberg K., Kopf M., and Kaufmann S.H. Lethal tuberculosis in interleukin-6-deficient mutant mice. Infect Immun 65 (1997) 4843-4849
64. Jones M.R., Quinton L.J., Simms B.T., Lupa M.M., Kogan M.S., and Mizgerd J.P. Roles of interleukin-6 in activation of STAT proteins and recruitment of neutrophils during Escherichia coli pneumonia. J Infect Dis 193 (2006) 360-369
65. Homann C., Hansen M.B., Graudal N., Hasselqvist P., Svenson M., Bendtzen K., et al. Anti-interleukin-6 autoantibodies in plasma are associated with an increased frequency of infections and increased mortality of patients with alcoholic cirrhosis. Scand J Immunol 44 (1996) 623-629
66. Graudal N.A., Svenson M., Tarp U., Garred P., Jurik A.G., and Bendtzen K. Autoantibodies against interleukin 1alpha in rheumatoid arthritis: association with long term radiographic outcome. Ann Rheum Dis 61 (2002) 598-602
67. Kopf M., Le Gros G., Coyle A.J., Kosco-Vilbois M., and Brombacher F. Immune responses of IL-4, IL-5, IL-6 deficient mice. Immunol Rev 148 (1995) 45-69
68. Faldt J., Wernstedt I., Fitzgerald S.M., Wallenius K., Bergstrom G., and Jansson J.O. Reduced exercise endurance in interleukin-6-deficient mice. Endocrinology 145 (2004) 2680-2686
69. Wallenius V., Wallenius K., Ahren B., Rudling M., Carlsten H., Dickson S.L., et al. Interleukin-6-deficient mice develop mature-onset obesity. Nat Med 8 (2002) 75-79
70. Wernstedt I., Edgley A., Berndtsson A., Faldt J., Bergstrom G., Wallenius V., et al. Reduced stress- and cold-induced increase in energy expenditure in interleukin-6-deficient mice. Am J Physiol Regul Integr Comp Physiol 291 (2006) R551-R557
71. Wernstedt I., Olsson B., Jernas M., Paglialunga S., Carlsson L.M., Smith U., et al. Increased levels of acylation-stimulating protein in interleukin-6-deficient (IL-6(-/-)) mice. Endocrinology 147 (2006) 2690-2695