title: Interleukin-13 protects against experimental autoimmune myocarditis by regulating macrophage differentiation.
abstract: We report here that interleukin (IL)-13 protects BALB/c mice from myocarditis, whether induced by peptide immunization or by viral infection. In contrast to mild disease in IL-4 knockout (KO) BALB/c mice, IL-13 KO BALB/c mice developed severe coxsackievirus B3 (CVB3)-induced autoimmune myocarditis and myocarditogenic peptide-induced experimental autoimmune myocarditis. Such severe disease was characterized by increased cardiac inflammation, increased total intracardiac CD45(+) leukocytes, elevated anti-cardiac myosin autoantibodies, and increased cardiac fibrosis. Echocardiography revealed that IL-13 KO mice developed severe dilated cardiomyopathy with impaired cardiac function and heart failure. Hearts of IL-13 KO mice had increased levels of the proinflammatory and profibrotic cytokines IL-1beta, IL-18, interferon-gamma, transforming growth factor-beta1, and IL-4 as well as histamine. The hallmark of the disease in IL-13 KO mice was the up-regulation of T-cell responses. CD4(+) T cells were increased in IL-13 KO hearts both proportionally and in absolute number. Splenic T cells from IL-13 KO mice were highly activated, and myosin stimulation additionally increased T-cell proliferation. CD4(+)CD25(+)Foxp3(+) regulatory T-cell numbers were decreased in the spleens of IL-13 KO mice. IL-13 deficiency led to decreased levels of alternatively activated CD206(+) and CD204(+) macrophages and increased levels of classically activated macrophages. IL-13 KO mice had increased caspase-1 activation, leading to increased production of both IL-1beta and IL-18. Therefore, IL-13 protects against myocarditis by modulating monocyte/macrophage populations and by regulating their function.
authors.affiliation: Johns Hopkins University, Department of Pathology, Division of Immunology, Ross 648, 720 Rutland Ave., Baltimore, MD 21205, USA. dcihako1@jhmi.edu
authors.forename: Daniela
authors.initials: D
authors.lastname: Cihakova
authors.forename: Jobert G
authors.initials: JG
authors.lastname: Barin
authors.forename: Marina
authors.initials: M
authors.lastname: Afanasyeva
authors.forename: Miho
authors.initials: M
authors.lastname: Kimura
authors.forename: DeLisa
authors.initials: D
authors.lastname: Fairweather
authors.forename: Michael
authors.initials: M
authors.lastname: Berg
authors.forename: Monica V
authors.initials: MV
authors.lastname: Talor
authors.forename: G Christian
authors.initials: GC
authors.lastname: Baldeviano
authors.forename: Sylvia
authors.initials: S
authors.lastname: Frisancho
authors.forename: Kathleen
authors.initials: K
authors.lastname: Gabrielson
authors.forename: Djahida
authors.initials: D
authors.lastname: Bedja
authors.forename: Noel R
authors.initials: NR
authors.lastname: Rose
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002311:Cardiomyopathy, Dilated / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation; D003384:Coxsackievirus Infections / Q000276:immunology / Q000378:metabolism*; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D006333:Heart Failure / Q000276:immunology / Q000378:metabolism; D018793:Interleukin-13 / Q000235:genetics / Q000502:physiology*; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009205:Myocarditis / Q000276:immunology / Q000378:metabolism*
chemical_list: D016207:Cytokines; D018793:Interleukin-13