Augmentation of pathogenesis of coxsackievirus B3 infections in mice by exogenous administration of interleukin-1 and interleukin-2.
Two variants of coxsackievirus B3 (CVB3) which differ dramatically in the ability to induce myocarditis in BALB/c mice were studied. H3 virus infection of murine monocytes in vitro resulted in release of concentrations of interleukin 1 (IL-1) and alpha/beta interferon that were high compared with those of cells infected with the H310A1 virus variant. In vivo, H3 virus infection caused substantial inflammatory cell infiltration of the myocardium, and lymphocytes from these animals gave predominantly Th1-cell responses to either whole H3 virus or overlapping peptides of the CVB3 vp1 capsid protein, as determined by IL-2 production. In contrast, H310A1 virus infection produced minimal myocarditis and Th1-cell responses, but Th2-cell activation was more pronounced than in H3 virus-infected mice (as determined by IL-4 concentrations). Exogenous treatment of H310A1 virus-infected mice with either IL-1 or IL-2 restored both myocarditis susceptibility and Th1-cell responses to whole virus and vp1 peptides. Furthermore, H310A1 virus-infected mice given exogenous IL-1 showed substantial in situ IL-2 deposition in the myocardium. These results indicate that CVB3-induced myocarditis may depend upon release of specific cytokines during infection and that activation of Th1 cells may be an important factor in pathogenesis.
Huber
S A
SA
Department of Pathology, University of Vermont, Burlington 05405.
Polgar
J
J
Schultheiss
P
P
Schwimmbeck
P
P
D000595:Amino Acid Sequence; D000818:Animals; D016827:CD8 Antigens / Q000276:immunology; D002213:Capsid / Q000276:immunology; D036022:Capsid Proteins; D002999:Clone Cells / Q000276:immunology; D003384:Coxsackievirus Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D016207:Cytokines / Q000494:pharmacology; D029822:Enterovirus B, Human / Q000276:immunology / Q000472:pathogenicity*; D006183:H-2 Antigens; D007375:Interleukin-1 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009205:Myocarditis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D009206:Myocardium / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014774:Virulence
D016827:CD8 Antigens; D036022:Capsid Proteins; D016207:Cytokines; D006183:H-2 Antigens; D007375:Interleukin-1; D007376:Interleukin-2; D010446:Peptide Fragments