Antibodies against IL-12 prevent superantigen-induced and spontaneous relapses of experimental autoimmune encephalomyelitis.
Immunization of (PL/J x SJL/J)F1 mice with myelin basic protein (MBP) induces relapsing experimental autoimmune encephalomyelitis (EAE). Relapses occur 7 to 10 days after recovery from the initial paralysis. Staphylococcal enterotoxins (SE) A or B, administered after recovery from the initial paralysis, induce immediate relapses. IL-12 is involved in the induction of EAE. Here, we show that SEA and SEB induce IL-12 in splenocytes from (PL/J x SJL/J)F1 mice in vitro and increase the level of IL-12 in the sera of mice treated with these superantigens. IL-12 administration mimics SE in inducing spontaneous relapses and in enhancing the severity and frequency of spontaneous relapses. IL-12 neutralization blocks SE-induced and subsequent relapses of EAE, and, when instituted after recovery from the initial attack, prevents spontaneous relapse. This is the first report of prevention of relapses of EAE with anti-IL-12 Ab, an approach which may prove useful in the prevention of exacerbations in multiple sclerosis.
Constantinescu
C S
CS
Department of Neurology, University of Pennsylvania, Philadelphia 19104, USA.
Wysocka
M
M
Hilliard
B
B
Ventura
E S
ES
Lavi
E
E
Trinchieri
G
G
Rostami
A
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D000942:Antigens, Bacterial / Q000276:immunology* / Q000633:toxicity; D001327:Autoimmune Diseases / Q000276:immunology / Q000517:prevention & control*; D001921:Brain / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D003711:Demyelinating Diseases; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000517:prevention & control*; D004768:Enterotoxins / Q000276:immunology* / Q000633:toxicity; D005260:Female; D006168:Guinea Pigs; D007114:Immunization; D007249:Inflammation; D018664:Interleukin-12 / Q000276:immunology / Q000502:physiology* / Q000633:toxicity; D008297:Male; D051379:Mice; D018716:Molecular Mimicry; D004676:Myelin Basic Protein / Q000276:immunology; D051381:Rats; D012008:Recurrence; D012720:Severity of Illness Index; D013116:Spinal Cord / Q000473:pathology; D013211:Staphylococcus aureus / Q000276:immunology; D018089:Superantigens / Q000276:immunology* / Q000633:toxicity; D018417:Th1 Cells / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D016207:Cytokines; D004768:Enterotoxins; D004676:Myelin Basic Protein; D018089:Superantigens; D018664:Interleukin-12; C026066:enterotoxin A, Staphylococcal; C031818:enterotoxin B, staphylococcal