Anti-IL-23 therapy inhibits multiple inflammatory pathways and ameliorates autoimmune encephalomyelitis

Journal of Clinical Investigation

Volumn 116, Issue 5, 2006, Pages 1317-1326

  Chen, Yi ^a   Langrish, Claire L ^a   Mckenzie, Brent ^a   Joyce Shaikh, Barbara ^a   Stumhofer, Jason S ^b   McClanahan, Terrill ^c   Blumenschein, Wendy ^c   Churakovsa, Tatyana ^d   Low, Justin ^d   Presta, Leonard ^d   Hunter, Christopher A ^b   Kastelein, Robert A ^a   Cua, Daniel J ^a,e  

^a Discovery Research   (United States)

^b UNIVERSITY OF PENNSYLVANIA   (United States)

^c Experimental Pathology and Pharmacology   (United States)

^d Schering Plough Biopharma   (United States)

^e MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

GAMMA INTERFERON; GAMMA INTERFERON INDUCIBLE PROTEIN 10; INTERLEUKIN 17; INTERLEUKIN 23; INTERLEUKIN 23P19 MONOCLONAL ANTIBODY; INTERLEUKIN 6; MESSENGER RNA; MONOCLONAL ANTIBODY; PROTEIN P19; PROTEOLIPID PROTEIN; STAT1 PROTEIN; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR T BET; TUMOR NECROSIS FACTOR; UNCLASSIFIED DRUG;

ALLERGIC ENCEPHALOMYELITIS; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; AUTOIMMUNE DISEASE; CENTRAL NERVOUS SYSTEM; CONTROLLED STUDY; EXPERIMENTAL MODEL; IMMUNIZATION; INFLAMMATION; MOUSE; NONHUMAN; PRIORITY JOURNAL;

ANIMALS; AUTOIMMUNE DISEASES; CHEMOKINES, CXC; DISEASE MODELS, ANIMAL; ENCEPHALOMYELITIS; FEMALE; INFLAMMATION; INTERFERON TYPE II; INTERLEUKIN-17; INTERLEUKIN-23; INTERLEUKIN-23 SUBUNIT P19; INTERLEUKIN-6; INTERLEUKINS; MULTIPLE SCLEROSIS; STAT1 TRANSCRIPTION FACTOR; T-LYMPHOCYTES; TUMOR NECROSIS FACTORS;

EID: 33646433989     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI25308     Document Type: Article

References (55)

1. Martino, G., and Hartung, H.P. 1999. Immunopathogenesis of multiple sclerosis: the role of T cells. Curr. Opin. Neurol. 12:309-321.
2. Behi, M.E., et al. 2005. New insights into cell responses involved in experimental autoimmune encephalomyelitis and multiple sclerosis. Immunol. Lett. 96:11-26.
3. O'Garra, A., and Arai, N. 2000. The molecular basis of T helper 1 and T helper 2 cell differentiation. Trends Cell Biol. 10:542-550.
4. Shtrichman, R., and Sanuel, C.E. 2001. The role of gamma interferon in antimicrobial immunity. Curr. Opin. Microbiol. 4:251-259.
5. Airoldi, I., et al. 2004. The IL-12Rβ2 gene functions as a tumor suppressor in human B cell malignancies. J. Clin. Invest. 113:1651-1659. doi:10.1172/JCI200420303.
6. Leonard, J.P., Waldburger, K.E., and Goldman, S.J. 1995. Prevention of experimental autoimmune encephalomyelitis by antibodies against interleukin 12. J. Exp. Med. 181:381-386.
7. Ichikawa, M., et al. 2000. Anti-IL-12 antibody prevents the development and progression of multiple sclerosis-like relapsing-remitting demyelinating disease in NOD mice induced with myelin oligodendrocyte glycoprotein peptide. J. Neuroimmunol. 102:56-66.
8. Constantinescu, C.S., et al. 1998. Antibodies against IL-12 prevent superantigen-induced and spontaneous relapses of experimental autoimmune encephalomyelitis. J. Immunol. 161:5097-5104.
9. Trembleau, S., Germann, T., Gately, M.K., and Adorini, L. 1995. The role of IL-12 in the induction of organ-specific autoimmune diseases. Immunol. Today. 16:383-386.
10. Adorini, L., Guery, J.C., and Trembleau, S. 1996. Manipulation of the Th1/Th2 cell balance: an approach to treat human autoimmune diseases? Autoimmunity. 23:53-68.
11. Leonard, J.P., Waldburger, K.E., and Goldman, S.J. 1996. Regulation of experimental autoimmune encephalomyelitis by interleukin-12. Ann. N. Y. Acad. Sci. 795:216-226.
12. McIntyre, K.W., et al. 1996. Reduced incidence and severity of collagen-induced arthritis in interleukin-12-deficient mice. Eur. J. Immunol. 26:2933-2938.
13. Malfait, A.M., et al. 1998. Blockade of IL-12 during the induction of collagen-induced arthritis (CIA) markedly attenuates the severity of the arthritis. Clin. Exp. Immunol. 111:377-383.
14. Ferber, I., et al. 1996. Mice with a disrupted IFN-gamma gene are susceptible to the induction of experimental autoimmune encephalomyelitis (EAE). J. Immunol. 156:5-7.
15. Willenborg, D.O., Fordham, S., Bernard, C.C., Cowden, W.B., and Ramshaw, I.A. 1996. IFN-gamma plays a critical down-regulatory role in the induction and effector phase of myelin oligodendrocyte glycoprotein-induced autoimmune encephalomyelitis. J. Immunol. 157:3223-3227.
16. Zhang, G., et al. 2003. Induction of experimental autoimmune encephalomyelitis in IL-12 receptor-beta 2-deficient mice: IL-12 responsiveness is not required in the pathogenesis of inflammatory demyelination in the central nervous system. J. Immunol. 170:2153-2160.
17. Becher, B., Durell, B.G., and Noelle, R.J. 2002. Experimental autoimmune encephalitis and inflammation in the absence of interleukin-12. J. Clin. Invest. 110:493-497. doi:10.1172/JCI200215751.
18. Gran, B., et al. 2002. IL-12p35-deficient mice are susceptible to experimental autoimmune encephalomyelitis: evidence for redundancy in the IL-12 system in the induction of central nervous system autoimmune demyelination. J. Immunol. 169:7104-7110.
19. Bettelli, E., et al. 2004. Loss of T-bet, but not STAT1, prevents the development of experimental autoimmune encephalomyelitis. J. Exp. Med. 200:79-87.
20. Chitnis, T., et al. 2001. Effect of targeted disruption of STAT4 and STAT6 on the induction of experimental autoimmune encephalomyelitis. J. Clin. Invest. 108:739-747. doi:10.1172/JCI200112563.
21. Oppmann, B., et al. 2000. Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity. 13:715-725.
22. Parham, C., et al. 2002. A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbeta1 and a novel cytokine receptor subunit, IL-23R. J. Immunol. 168:5699-5708.
23. Cua, D.J., et al. 2003. Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature. 421:744-748.
24. Murphy, C.A., et al. 2003. Divergent pro- and antiinflammatory roles for IL-23 and IL-12 in joint autoimmune inflammation. J. Exp. Med. 198:1951-1957.
25. Langrish, C.L., et al. 2005. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J. Exp. Med. 201:233-240.
26. Yen, D., et al. 2006. IL-23 is essential for T cell-mediated colitis and promotes inflammation via IL-17 and IL-6. J. Clin. Invest. 116:1310-1316.
27. Brok, H.P., et al. 2002. Prevention of experimental autoimmune encephalomyelitis in common marmosets using an anti-IL-12p40 monoclonal antibody. J. Immunol. 169:6554-6563.
28. Sedgwick, J.D., et al. 1991. Isolation and direct characterization of resident microglial cells from the normal and inflamed central nervous system. Proc. Natl. Acad. Sci. U. S. A. 88:7438-7442.
29. Hickey, W.F. 1991. Migration of hematogenous cells through the blood-brain barrier and the initiation of CNS inflammation. Brain Pathol. 1:97-105.
30. Kennedy, M.K., Torrance, D.S., Picha, K.S., and Mohler, K.M. 1992. Analysis of cytokine mRNA expression in the central nervous system of mice with experimental autoimmune encephalomyelitis reveals that IL-10 mRNA expression correlates with recovery. J. Immunol. 149:2496-2505.
31. Refaeli, Y., Van Parijs, L., Alexander, S.I., and Abbas, A.K. 2002. Interferon gamma is required for activation-induced death of T lymphocytes. J. Exp. Med. 196:999-1005.
32. Monney, L., et al. 2002. Th1-specific cell surface protein Tim-3 regulates macrophage activation and severity of an autoimmune disease. Nature. 415:536-541.
33. McMahon, E.J., Bailey, S.L., Castenada, C.V., Waldner, H., and Miller, S.D. 2005. Epitope spreading initiates in the CNS in two mouse models of multiple sclerosis. Nat. Med. 11:335-339.
34. Langrish, C.L., et al. 2004. IL-12 and IL-23: master regulators of innate and adaptive immunity. Immunol. Rev. 202:96-105.
35. McKenzie, B.S., Kastelein, R.A., and Cua, D.J. 2005. Understanding the IL-23/IL-17 immune pathway. Trends Immunol. 27:17-23.
36. Harrington, L.E., et al. 2005. Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat. Immunol. 6:1123-1132.
37. Park, H., et al. 2005. A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat. Immunol. 6:1133-1141.
38. Afkarian, M., et al. 2002. T-bet is a STAT1-induced regulator of IL-12R expression in naive CD4+ T cells. Nat. Immunol. 3:549-557.
39. Lovett-Racke, A.E., et al. 2004. Silencing T-bet defines a critical role in the differentiation of autoreactive T lymphocytes. Immunity. 21:719-731.
40. Lugo-Villarino, G., Maldonado-Lopez, R., Possemato, R., Penaranda, C., and Glimcher, L.H. 2003. T-bet is required for optimal production of IFN-gamma and antigen-specific T cell activation by dendritic cells. Proc. Natl. Acad. Sci. U. S. A. 100:7749-7754.
41. Gielen, A.W., et al. 2005. Expression of T cell immunoglobulin- and mucin-domain-containing molecules-1 and -3 (TIM-1 and -3) in the rat nervous and immune systems. J. Neuroimmunol. 164:93-104.
42. Bettelli, E., and Kuchroo, V.K. 2005. IL-12- and IL-23-induced T helper cell subsets: birds of the same feather flock together. J. Exp. Med. 201:169-171.
43. Hwang, E.S., Szabo, S.J., Schwartzberg, P.L., and Glimcher, L.H. 2005. T helper cell fate specified by kinase-mediated interaction of T-bet with GATA-3. Science. 307:430-433.
44. Billiau, A., et al. 1988. Enhancement of experimental allergic encephalomyelitis in mice by antibodies against IFN-gamma. J. Immunol. 140:1506-1510.
45. Muhl, H., and Pfeilschifter, J. 2003. Anti-inflammatory properties of pro-inflammatory interferon-gamma. Int. Immunopharmacol. 3:1247-1255.
46. Novelli, F., et al. 1997. Expression and role in apoptosis of the alpha- and beta-chains of the IFN-gamma receptor on human Th1 and Th2 clones. J. Immunol. 159:206-213.
47. Belladonna, M.L., et al. 2002. IL-23 and IL-12 have overlapping, but distinct, effects on murine dendritic cells. J. Immunol. 168:5448-5454.
48. Khader, S.A., et al. 2005. IL-23 compensates for the absence of IL-12p70 and is essential for the IL-17 response during tuberculosis but is dispensable for protection and antigen-specific IFN-gamma responses if IL-12p70 is available. J. Immunol. 175:788-795.
49. Lieberman, L.A., et al. 2004. IL-23 provides a limited mechanism of resistance to acute toxoplasmosis in the absence of IL-12. J. Immunol. 173:1887-1893.
50. Happel, K.I., et al. 2003. Cutting edge: roles of Toll-like receptor 4 and IL-23 in IL-17 expression in response to Klebsiella pneumoniae infection: requirement of interleukin 17 receptor signaling for lung CXC chemokine and granulocyte colony-stimulating factor expression, neutrophil recruitment, and host defense. J. Immunol. 170:4432-4436.
51. Ye, P., et al. 2001. Requirement of interleukin 17 receptor signaling for lung CXC chemokine and granulocyte colony-stimulating factor expression, neutrophil recruitment, and host defense. J. Exp. Med. 194:519-527.
52. Miyamoto, M., et al. 2003. Endogenous IL-17 as a mediator of neutrophil recruitment caused by endotoxin exposure in mouse airways. J. Immunol. 170:4665-4672.
53. Stark, M.A., et al. 2005. Phagocytosis of apoptotic neutrophils regulates granulopoiesis via IL-23 and IL-17. Immunity. 22:285-294.
54. Kauffman, C.L., et al. 2004. A phase I study evaluating the safety, pharmacokinetics, and clinical response of a human IL-12 p40 antibody in subjects with plaque psoriasis. J. Invest. Dermatol. 123:1037-1044.
55. Mannon, P.J., et al. 2004. Anti-interleukin-12 antibody for active Crohn's disease. N. Engl. J. Med. 351:2069-2079.