Effects of methyl mercury on cytokines, inflammation and virus clearance in a common infection (coxsackie B3 myocarditis).
A myocarditic coxsackievirus B3 (CB3) infection in Balb/c mice was used to investigate the effects of 12 weeks of methyl mercury (MeHg) exposure (3.69 mg/g diet) on inflammatory heart lesions, virus in the heart, the cytokine response, i.e. cachectin/TNF-alpha and gamma-interferon (IFN-gamma) levels in plasma, and on disease complications and mortality. This dose of MeHg did not influence mortality in this infection model. The inflammatory and necrotic lesions in the ventricular myocardium 7 days after the inoculation covered 2.2% of the tissue section area in infected control mice. This damage was increased (n.s.) by 50% (to 3.3% of the tissue section area) in MeHg-treated mice. The response pattern of lymphocyte subsets in situ in myocardial inflammatory lesions was corroborated using an immune histological technique. MeHg treatment tended to increase (2.2-fold, n.s.) the number of Mac 2+ cells (macrophages) in the heart muscle in this infection. Plasma levels of both TNF-alpha and IFN-gamma increased on day 3 of the infection in MeHg-treated as well as in non-MeHg-treated mice, but the mean IFN-gamma response was more pronounced in the MeHg-treated mice. On day 7 of the infection, when most animals still showed clinical signs of disease, cytokine levels were back to normal. MeHg-exposure in non-infected mice did not affect cytokine levels. In situ hybridization of virus RNA in myocardial tissue showed remaining virus in those mice who had the lowest plasma IFN-gamma levels. A 20% increased (P < 0.05) lymphoproliferative response to the T cell mitogen Con A was observed as a result of the MeHg treatment. Even heart tissue lesions and virus persistence tended to be influenced by MeHg in a direction compatible with the development of chronic disease.
Ilbäck
N G
NG
Pharmacia and UpJohn, Helsingborg, Sweden.
Wesslén
L
L
Fohlman
J
J
Friman
G
G
D000818:Animals; D009202:Cardiomyopathies / Q000473:pathology* / Q000821:virology; D003384:Coxsackievirus Infections / Q000401:mortality / Q000503:physiopathology*; D029822:Enterovirus B, Human / Q000302:isolation & purification*; D005260:Female; D006321:Heart / Q000821:virology; D007249:Inflammation / Q000473:pathology; D007371:Interferon-gamma / Q000097:blood*; D008767:Methylmercury Compounds / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D009206:Myocardium / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*
D008767:Methylmercury Compounds; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma