Interleukin-12 enhances clinical experimental autoimmune myasthenia gravis in susceptible but not resistant mice.
Experimental autoimmune myasthenia gravis (EAMG) is induced by antibodies against the nicotinic acetylcholine receptor (AChR). Studies indicate a role for interferon-gamma (IFN-gamma) in EAMG. We examined the effect of IL-12, a major inducer of IFN-gamma production, on EAMG in C57BL/6 mice. Five doses of IL-12 accelerated and enhanced clinical disease in AChR-immunized mice. Control B6 mice, IFN-gamma gene-knockout mice, and EAMG-resistant bm12 mice showed no enhancement of disease. Shifting to a Th1-type antibody isotype distribution was insufficient to cause disease. Other factors, such as direct effects of Th1 cytokines on muscle tissue, may be involved in EAMG susceptibility.
Sitaraman
S
S
Department of Pediatrics, University of Texas Health Science Center at San Antonio, San Antonio, TX 78284, USA.
Metzger
D W
DW
Belloto
R J
RJ
Infante
A J
AJ
Wall
K A
KA
D000818:Animals; D020274:Autoimmune Diseases of the Nervous System / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D004198:Disease Susceptibility; D005260:Female; D007132:Immunoglobulin Isotypes / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics / Q000502:physiology; D018664:Interleukin-12 / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL / Q000235:genetics; D018345:Mice, Knockout / Q000235:genetics; D009132:Muscles / Q000294:innervation / Q000473:pathology; D009157:Myasthenia Gravis / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D009410:Nerve Degeneration / Q000473:pathology; D009416:Nerve Regeneration; D011950:Receptors, Cholinergic / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology
D007132:Immunoglobulin Isotypes; D011950:Receptors, Cholinergic; D018664:Interleukin-12; D007371:Interferon-gamma