Prevention of experimental autoimmune encephalomyelitis in common marmosets using an anti-IL-12p40 monoclonal antibody.
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.
Brok
Herbert P M
HP
Department of Immunobiology, Biomedical Primate Research Center, Rijswijk, The Netherlands.
van Meurs
Marjan
M
Blezer
Erwin
E
Schantz
Allen
A
Peritt
David
D
Treacy
George
G
Laman
Jon D
JD
Bauer
Jan
J
't Hart
Bert A
BA
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000276:immunology; D001921:Brain / Q000276:immunology / Q000473:pathology; D002144:Callithrix; D003429:Cross Reactions; D016207:Cytokines / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D018664:Interleukin-12 / Q000037:antagonists & inhibitors*; D053762:Interleukin-12 Subunit p40; D009103:Multiple Sclerosis / Q000209:etiology / Q000276:immunology; D009185:Myelin Proteins / Q000276:immunology; D021122:Protein Subunits / Q000037:antagonists & inhibitors*; D013116:Spinal Cord / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D016207:Cytokines; D053762:Interleukin-12 Subunit p40; D009185:Myelin Proteins; D021122:Protein Subunits; D018664:Interleukin-12