Effects of early IL-17A neutralization on disease induction in a primate model of experimental autoimmune encephalomyelitis.
We report on the effect of antibody-mediated neutralization of interleukin (IL)-17A in a non-human primate experimental autoimmune encephalomyelitis (EAE) model induced with recombinant human myelin oligodendrocyte glycoprotein (rhMOG). We tested a human-anti-human IL-17A-antibody in two doses (3 and 30 mg/kg) against placebo (PBS). The treatment was started 1 day before EAE induction and continued throughout the experiment. Although all monkeys developed clinically evident EAE, the onset of neurological signs was delayed in some monkeys from both treatment groups. Total CNS lesion volumes, demyelination, or inflammation did not differ between the different groups. Immune profiling revealed an altered distribution of IL-17A producing cells in the lymphoid organs of antibody-treated monkeys. Comparable numbers of IL-17A producing cells were observed in the brain. RhMOG-induced T cell proliferation in the lymph nodes was slightly reduced after anti-IL-17A antibody treatment. To summarize, we found that anti-IL-17A antibody as a single treatment from disease induction effects a trend towards delayed neurological disease progression in the marmoset EAE model, although the effect did not reach statistical significance. This suggests a role of IL-17A in late stage disease in the marmoset EAE model, but IL-17A may not be the dominant pathogenic cytokine.
Kap
Yolanda S
YS
Department of Immunobiology, Biomedical Primate Research Centre, P.O. Box 3306 2280 GH, Rijswijk, The Netherlands.
Jagessar
S Anwar
SA
van Driel
Nikki
N
Blezer
Erwin
E
Bauer
Jan
J
van Meurs
Marjan
M
Smith
Paul
P
Laman
Jon D
JD
't Hart
Bert A
BA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001921:Brain / Q000276:immunology / Q000473:pathology; D002144:Callithrix; D049109:Cell Proliferation / Q000187:drug effects; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020381:Interleukin-17 / Q000037:antagonists & inhibitors* / Q000276:immunology; D008297:Male; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D013601:T-Lymphocytes / Q000276:immunology
D000911:Antibodies, Monoclonal; D020381:Interleukin-17; C571326:MOG protein, human; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein