Prevention of experimental autoimmune encephalomyelitis in common marmosets using an anti-IL-12p4O monoclonal antibody

被引:103
作者
Brok, HPM
van Meurs, M
Blezer, E
Schantz, A
Peritt, D
Treacy, G
Laman, JD
Bauer, J
't Hart, BA
机构
[1] Biomed Primate Res Ctr, Dept Immunobiol, NL-2288 GJ Rijswijk, Netherlands
[2] Erasmus MC, Dept Immunol, Rotterdam, Netherlands
[3] Univ Med Ctr, Image Sci Inst, Dept Expt In Vivo NMR, Utrecht, Netherlands
[4] Centocor Inc, Dept Res & Dev, Malvern, PA 19355 USA
[5] Univ Vienna, Brain Sci Inst, Div Neuroimmunol, Vienna, Austria
[6] Univ Utrecht, Dept Pharmacol & Pathobiol, Utrecht, Netherlands
关键词
D O I
10.4049/jimmunol.169.11.6554
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The experimental autoimmune encephalomyelitis (EAE) model in the common marmoset approximates recognized features of the human disease multiple sclerosis (MS) with regard to its clinical presentation as well as neuropathological and radiological aspects of the lesions in brain and spinal cord. IL-12 is a proinflammatory cytokine that is produced by APC and promotes differentiation of Th1 effector cells. IL-12 is produced in the developing lesions of patients with MS as well as in EAE-affected animals. Previously it was shown that interference in IL-12 pathways effectively prevents EAE in rodents. In this study we report that in vivo neutralization of IL-12p40 using a novel Ab has beneficial effects in the myelin-induced EAE model in common marmosets. The Ab was injected i.v. at 7-day intervals starting well after immunization (day 14) and was continued until the end of the study (day 86). Stable levels of the Ab were measured 3 days after each injection throughout the study period. During this period anti-Ab responses could not be detected. We demonstrate that anti-IL-12p40 treatment has a protective effect on the neurological dysfunction as well as on neuropathological changes normally observed in the brain and spinal cord of EAE-affected individuals.
引用
收藏
页码:6554 / 6563
页数:10
相关论文
共 67 条
  • [1] Myelin/axonal pathology in interleukin-12 induced serial relapses of experimental allergic encephalomyelitis in the Lewis rat
    Ahmed, Z
    Gveric, D
    Pryce, G
    Baker, D
    Leonard, JP
    Cuzner, ML
    [J]. AMERICAN JOURNAL OF PATHOLOGY, 2001, 158 (06) : 2127 - 2138
  • [2] The common marmoset:: A new world primate species with limited Mhc class II variability
    Antunes, SG
    de Groot, NG
    Brok, H
    Doxiadis, G
    Menezes, AAL
    Otting, N
    Bontrop, RE
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (20) : 11745 - 11750
  • [3] Defective regulation of IFNγ and IL-12 by endogenous IL-10 in progressive MS
    Balashov, KE
    Comabella, M
    Ohashi, T
    Khoury, SJ
    Weiner, HL
    [J]. NEUROLOGY, 2000, 55 (02) : 192 - 198
  • [4] Increased interleukin 12 production in progressive multiple sclerosis: Induction by activated CD4(+) T cells via CD40 ligand
    Balashov, KE
    Smith, DR
    Khoury, SJ
    Hafler, DA
    Weiner, HL
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (02) : 599 - 603
  • [5] Soluble tumor necrosis factor receptor inhibits interleukin 12 production by stimulated human adult microglial cells in vitro
    Becher, B
    Dodelet, V
    Fedorowicz, V
    Antel, JP
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1996, 98 (07) : 1539 - 1543
  • [6] CD40 engagement stimulates IL-12 p70 production by human microglial cells: basis for Th1 polarization in the CNS
    Becher, B
    Blain, M
    Antel, JP
    [J]. JOURNAL OF NEUROIMMUNOLOGY, 2000, 102 (01) : 44 - 50
  • [7] Major histocompatibility complex class II polymorphisms in primates
    Bontrop, RE
    Otting, N
    de Groot, NG
    Doxiadis, GGM
    [J]. IMMUNOLOGICAL REVIEWS, 1999, 167 : 339 - 350
  • [8] Prevention of experimental autoimmune encephalomyelitis in the common marmoset (Callithrix jacchus) using a chimeric antagonist monoclonal antibody against human CD40 is associated with altered B cell responses
    Boon, L
    Brok, HPM
    Bauer, J
    Ortiz-Buijsse, A
    Schellekens, MM
    Ramdien-Murli, S
    Blezer, E
    van Meurs, M
    Ceuppens, J
    de Boer, M
    't Hart, BA
    Laman, JD
    [J]. JOURNAL OF IMMUNOLOGY, 2001, 167 (05) : 2942 - 2949
  • [9] Bright JJ, 1998, J IMMUNOL, V161, P7015
  • [10] Expression of IL-12 in CNS and lymphoid organs of mice with experimental allergic encephalitis
    Bright, JJ
    Musuro, BF
    Du, C
    Sriram, S
    [J]. JOURNAL OF NEUROIMMUNOLOGY, 1998, 82 (01) : 22 - 30