Nasal administration of cardiac myosin suppresses autoimmune myocarditis in mice.
OBJECTIVE
This study was designed to examine whether myocarditis induced in a mouse model can be effectively suppressed by nasal administration of cardiac myosin (CM).


BACKGROUND
Myocarditis in humans often follows viral infection and is accompanied by evidence of an autoimmune response to CM. Treatment has been hampered by the fact that measures undertaken to reduce the autoimmune response often enhance the viral infection. Delivery of antigen via nasal route has been shown to induce antigen-specific tolerance and suppress certain autoimmune diseases in animal models.


METHODS
Myocarditis was induced in A/J mice by two subcutaneous injections of CM emulsified in complete Freund's adjuvant. Nasal instillation of CM (200 microg/mouse) or vehicle buffer was carried out three days before the first subcutaneous injection (day -3). The effect of nasal instillation of CM on cardiac histopathology, cytokine production by splenocytes, and antibody response was examined three weeks after the first subcutaneous injection (day 21).


RESULTS
Nasal administration of CM effectively reduced the severity of myocarditis. Consistent with the histological findings, the levels of interleukin-2 (IL-2), tumor necrosis factor-alpha, and IL-1beta produced by splenocytes in response to CM were significantly decreased. In addition, the serum levels of IgE and IgG1 anti-myosin antibodies were suppressed. However, the levels of transforming growth factor-beta (TGF-beta) and CM-specific IgA antibodies were not affected.


CONCLUSIONS
Taken together, our results do not support active suppression through upregulation of TGF-beta, IL-4, and IL-10 as a mechanism of tolerance, but favor anergy or deletion of both Th1 and Th2 autoreactive T cells.
Wang
Y
Y
Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
Afanasyeva
M
M
Hill
S L
SL
Kaya
Z
Z
Rose
N R
NR
D000281:Administration, Intranasal; D000818:Animals; D001327:Autoimmune Diseases / Q000517:prevention & control*; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007108:Immune Tolerance; D051379:Mice; D008815:Mice, Inbred Strains; D009205:Myocarditis / Q000276:immunology / Q000517:prevention & control*; D009218:Myosins / Q000008:administration & dosage*; D016212:Transforming Growth Factor beta / Q000627:therapeutic use*
D016207:Cytokines; D016212:Transforming Growth Factor beta; D009218:Myosins