Cytokine expression in murine cytomegalovirus-induced myocarditis: modulation with interferon-alpha therapy.
Cytomegalovirus-induced myocarditis is largely immune-mediated. BALB/c mice produced higher levels of IL-4 in the heart indicative of a Th2-like response. Although IL-6, IL-10, IL-18, and TNF-alpha were produced in the heart during acute infection, BALB/c mice lacked a substantial IL-2 and IFN-gamma response. Conversely, C57BL/6 mice produced significant levels of IFN-gamma in the heart with no significant levels of IL-4 or IL-6, suggestive of a dominant Th1-like response to virus infection. IFN-alpha/beta immunotherapy is known to suppress the development of MCMV-myocarditis. Cytokine secretion in IFN-stimulated MCMV-infected BALB/c myocytes was found to be IFN subtype-dependent with elevation of IL-6 and IL-18 levels. During the chronic phase of disease, IFNA6 DNA treatment in vivo increased IL-18 production in the heart. These results suggest that IFN subtype therapy may have immunomodulating effects in reducing disease severity in BALB/c mice via regulation of cytokine production in the heart.
Lenzo
Jason C
JC
Division of Health Sciences, Murdoch University, South Street, Perth 6150, Australia.
Mansfield
Josephine P
JP
Sivamoorthy
Soruba
S
Cull
Vanessa S
VS
James
Cassandra M
CM
D000818:Animals; D019556:COS Cells; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology*; D006566:Herpesviridae Infections / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D007167:Immunotherapy; D016898:Interferon-alpha / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018146:Muromegalovirus / Q000276:immunology* / Q000472:pathogenicity; D009205:Myocarditis / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D009206:Myocardium / Q000276:immunology / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000276:immunology / Q000821:virology; D010957:Plasmids / Q000235:genetics / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D014162:Transfection
D016207:Cytokines; D016898:Interferon-alpha