Elsevier

Cellular Immunology

Volume 213, Issue 1, 10 October 2001, Pages 52-61
Cellular Immunology

Regular Article
Immunomodulation of Murine Cytomegalovirus-Induced Myocarditis in Mice Treated with Lipopolysaccharide and Tumor Necrosis Factor

https://doi.org/10.1006/cimm.2001.1859Get rights and content

Abstract

Murine cytomegalovirus (MCMV) infection of BALB/c mice produces acute and chronic myocarditis similar to clinical disease in humans. In contrast, MCMV-infected C57BL/6 mice develop only mild acute myocarditis. We have investigated the effect of administration of the immunomodulator lipopolysaccharide (LPS) on the development of postviral myocarditis in mice. LPS exacerbated heart inflammation in both strains of MCMV-infected mice, with normally resistant C57BL/6 mice developing chronic myocarditis. Autoantibodies to cardiac myosin were enhanced with LPS treatment in both MCMV-infected mouse strains. LPS treatment also increased the production of TNF in the sera without affecting virus titers in the spleen, liver, or salivary glands, a target organ most affected during persistent virus infection. In LPS/MCMV-infected BALB/c mice, TNF, IL-6, and IL-10 levels were detected in cultures of heart infiltrating cells but not in splenocytes. Importantly, administration of the bioactive synthetic TNF peptide (amino acids 114–130) increased myocarditis in C57BL/6 mice, similar to that seen with LPS treatment. TNF peptide/MCMV-infected BALB/c and C57BL/6 mice showed distinct differences in the expression pattern of IFN-γ, IL-10, and TNF. These data show that the disease may be partly regulated by TNF among other select cytokines and autoantibodies to cardiac myosin. The immunopathological nature of MCMV-induced myocarditis is thus highlighted.

References (32)

  • E. Arbustini et al.

    Histopathologic profile of human cytomegalovirus infections in patients with heart transplants

    Am. J. Clin. Pathol.

    (1992)
  • H. Ando et al.

    Dilated cardiomyopathy caused by cytomegalovirus infection in a renal transplant recipient

    Jpn. Heart J.

    (1992)
  • B. Maisch et al.

    Cytomegalovirus associated inflammatory heart muscle disease

    Scand. J. Infect. Dis. Suppl.

    (1993)
  • W.N. Bartholomaeus et al.

    Multiple autoantibodies following cytomegalovirus infection: Virus distribution and specificity of autoantibodies

    Immunology

    (1988)
  • C.M. Lawson et al.

    Genetic control of mouse cytomegalovirus-induced myocarditis

    Immunology

    (1990)
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    This work was supported by the Australian National Health and Medical Research Council (Project Grants 961312 and 000264).

    2

    Current address: Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205.

    3

    To whom correspondence and reprint requests should be addressed Dr Cassandra M Lawson, Division of Veterinary and Biomedical Sciences, Murdoch University, Perth 6150, Australia. Fax: 618 9310 4144. E-mail: [email protected].

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