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
  • [11] Myelin/oligodendrocyte glycoprotein-induced autoimmune encephalomyelitis in common marmosets: The encephalitogenic T cell epitope pMOG24-36 is presented by a monomorphic MHC class II molecule
    Brok, HPM
    Uccelli, A
    de Rosbo, NK
    Bontrop, RE
    Roccatagliata, L
    de Groot, NG
    Capello, E
    Laman, JD
    Nicolay, K
    Mancardi, GL
    Ben-Nun, A
    't Hart, BA
    [J]. JOURNAL OF IMMUNOLOGY, 2000, 165 (02) : 1093 - 1101
  • [12] Non-human primate models of multiple sclerosis
    Brok, HPM
    Bauer, J
    Jonker, M
    Blezer, E
    Amor, S
    Bontrop, RE
    Laman, JD
    't Hart, BA
    [J]. IMMUNOLOGICAL REVIEWS, 2001, 183 : 173 - 185
  • [13] Role of costimulation in the induction of the IL-12/PL-12 receptor pathway and the development of autoimmunity
    Chang, JT
    Segal, BM
    Shevach, EM
    [J]. JOURNAL OF IMMUNOLOGY, 2000, 164 (01) : 100 - 106
  • [14] Antibody humanization: a case of the 'Emperor's new clothes'?
    Clark, M
    [J]. IMMUNOLOGY TODAY, 2000, 21 (08): : 397 - 402
  • [15] IL-12 reverses the suppressive effect of the CD40 ligand blockade on experimental autoimmune encephalomyelitis (EAE)
    Constantinescu, CS
    Hilliard, B
    Wysocka, M
    Ventura, ES
    Bhopale, MK
    Trinchieri, G
    Rostami, AM
    [J]. JOURNAL OF THE NEUROLOGICAL SCIENCES, 1999, 171 (01) : 60 - 64
  • [16] Modulation of susceptibility and resistance to an autoimmune model of multiple sclerosis in prototypically susceptible and resistant strains by neutralization of interleukin-12 and interleukin-4, respectively
    Constantinescu, CS
    Hilliard, B
    Ventura, E
    Wysocka, M
    Showe, L
    Lavi, E
    Fujioka, T
    Scott, P
    Trinchieri, G
    Rostami, A
    [J]. CLINICAL IMMUNOLOGY, 2001, 98 (01) : 23 - 30
  • [17] Astrocytes and microglia produce interleukin-12 p40
    Constantinescu, CS
    Frei, K
    Wysocka, M
    Trinchieri, G
    Malipiero, U
    Rostami, A
    Fontana, A
    [J]. INERLEUKIN 12: CELLULAR AND MOLECULAR IMMUNOLOGY OF AN IMPORTANT REGULATORY CYTOKINE, 1996, 795 : 328 - 333
  • [18] Constantinescu CS, 1998, J IMMUNOL, V161, P5097
  • [19] Inhibition of CD40 signaling pathway by tyrphostin A1 reduces secretion of IL-12 in macrophage, Th1 cell development and experimental allergic encephalomyelitis in SJL/J mice
    Du, C
    Bright, JJ
    Sriram, S
    [J]. JOURNAL OF NEUROIMMUNOLOGY, 2001, 114 (1-2) : 69 - 79
  • [20] Increased release of interleukin-12p40 in MS - Association with intracerebral inflammation
    Fassbender, K
    Ragoschke, A
    Rossol, S
    Schwartz, A
    Mielke, O
    Paulig, A
    Hennerici, M
    [J]. NEUROLOGY, 1998, 51 (03) : 753 - 758