Interleukin-6-deficient mice resist development of autoimmune myocarditis associated with impaired upregulation of complement C3.
BACKGROUND
Interleukin (IL)-6 regulates various aspects of the immune response. In the context of heart diseases, it has been recognized as a prognostic factor for dilated cardiomyopathy, which often results from myocarditis.


RESULTS
Using IL-6-deficient mice, we studied the role of IL-6 in a model of autoimmune myocarditis resulting from immunization with a peptide derived from cardiac alpha-myosin. Prevalence and severity of myocarditis were markedly reduced in the absence of IL-6. CD4+ T cells from immunized IL-6-deficient mice proliferated poorly on restimulation with specific antigen in vitro and did not mediate disease on adoptive transfer into IL-6-competent RAG-2-deficient mice, which otherwise lack B cells and T cells. Production of complement C3, a crucial factor for the development of myocarditis, was strongly upregulated in IL-6+/+ but not in IL-6-deficient mice after immunization.


CONCLUSIONS
Our results demonstrate that IL-6 is required for the expansion of autoimmune CD4+ T cells and the pathogenesis of autoimmune myocarditis, possibly by upregulation of complement C3.
Eriksson
Urs
U
Department of Internal Medicine, Medical ICU, University Hospital, Basel, Switzerland. ueriksson@uhbs.ch
Kurrer
Michael O
MO
Schmitz
Nicole
N
Marsch
Stephan C
SC
Fontana
Adriano
A
Eugster
Hans-Pietro
HP
Kopf
Manfred
M
D019264:Adoptive Transfer; D000818:Animals; D001323:Autoantibodies / Q000097:blood; D001327:Autoimmune Diseases / Q000150:complications / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D003176:Complement C3 / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D004195:Disease Models, Animal; D004198:Disease Susceptibility / Q000276:immunology; D007114:Immunization; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009205:Myocarditis / Q000150:complications / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000276:immunology / Q000473:pathology; D010446:Peptide Fragments / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D015854:Up-Regulation; D024723:Ventricular Myosins / Q000276:immunology
D001323:Autoantibodies; D003176:Complement C3; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D010446:Peptide Fragments; C499308:Rag2 protein, mouse; D014409:Tumor Necrosis Factor-alpha; C064655:V(D)J recombination activating protein 2; D024723:Ventricular Myosins