Cutting edge: a critical role for IL-10 in induction of nasal tolerance in experimental autoimmune myocarditis.
Appropriate treatment of autoimmune myocarditis following virus infection remains a major clinical problem. Induction of nasal tolerance may provide a new approach to treatment. However, the exact mechanism of nasal tolerance is unknown. To assess the mechanism of nasal tolerance, we examined the role of IL-10 in the induction and suppression of autoimmune myocarditis. First we showed that blocking IL-10 concurrent with nasal administration of Ag abolished the disease-suppressing effect of nasal tolerization. It also led to increased cardiac myosin-specific IL-1 and TNF-alpha production. Then we demonstrated that blocking IL-10 during the effector phase increased not only the incidence and severity of disease but also Ag-specific IL-2, IL-4, and TNF-alpha production as well as cardiac myosin-specific IgG1 and IgG2b production, whereas blocking IL-10 during the induction phase had no effect. This study implicates IL-10 in the induction of nasal tolerance and in limiting inflammation later during the disease process.
Kaya
Ziya
Z
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21205, USA.
Dohmen
K Malte
KM
Wang
Yan
Y
Schlichting
Jens
J
Afanasyeva
Marina
M
Leuschner
Florian
F
Rose
Noel R
NR
D000281:Administration, Intranasal; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001323:Autoantibodies / Q000096:biosynthesis; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D024722:Cardiac Myosins / Q000008:administration & dosage / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D007108:Immune Tolerance; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D007700:Kinetics; D051379:Mice; D009205:Myocarditis / Q000276:immunology* / Q000473:pathology
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D016207:Cytokines; D016753:Interleukin-10; D024722:Cardiac Myosins