title: Characterization of cytokine and iNOS mRNA expression in situ during the course of experimental autoimmune myocarditis in rats.
abstract: Ribonuclease protection assay was used to demonstrate mRNA expression of several cytokines as well as inducible NO synthase (iNOS), constitutive endothelial NO synthase (cNOS) and perforin in the myocardium during the course of experimental autoimmune myocarditis (EAM) in rats. Interleukin 2 (IL-2) appeared in the initial inflammatory phase (day 14), subsided in the maximum inflammatory phase (day 19) and disappeared by the recovery phase (day 25). mRNA of IL-3 beta, interferon gamma INF-gamma and tumor necrosis factor alpha (TNF-alpha) were detected only in the maximum inflammatory phase and iNOS also appeared for several days at this time. In contrast. IL-10 mRNA was detected after the maximum inflammatory stage and persisted into the recovery phase (days 25-36). Although transforming growth factor beta 1 (TGF-beta 1) could be detected in all phases, the expression was markedly enhanced in the maximum inflammatory phase and gradually diminished (around day 36) to basal levels. Perforin mRNA was not detected at any point in the disease. Besides macrophages and CD4 T cells, a number of neutrophils were found in the myocardium especially at peak inflammatory stage. We suggest that antigen (Ag) primed Ag presenting cells or macrophages interact with T cells (Th1) to produce IL-2 and subsequent IFN-gamma, which further activates macrophages in the myocardium. Consequently, TNF-alpha and iNOS may inflict tissue damage to myocardium. It is also suggested that TGF-beta) and one representative Th2 cytokine, IL-10, help inhibit inflammation. These findings suggest that Th1 and Th2 cytokines are produced at different stages of EAM and modulate the inflammation and the course of EAM.
authors.affiliation: Department of Immunology, Niigata University School of Medicine, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Okura
authors.forename: T
authors.initials: T
authors.lastname: Yamamoto
authors.forename: S
authors.initials: S
authors.lastname: Goto
authors.forename: T
authors.initials: T
authors.lastname: Inomata
authors.forename: S
authors.initials: S
authors.lastname: Hirono
authors.forename: H
authors.initials: H
authors.lastname: Hanawa
authors.forename: L
authors.initials: L
authors.lastname: Feng
authors.forename: C B
authors.initials: CB
authors.lastname: Wilson
authors.forename: I
authors.initials: I
authors.lastname: Kihara
authors.forename: T
authors.initials: T
authors.lastname: Izumi
authors.forename: A
authors.initials: A
authors.lastname: Shibata
authors.forename: Y
authors.initials: Y
authors.lastname: Aizawa
authors.forename: S
authors.initials: S
authors.lastname: Seki
authors.forename: T
authors.initials: T
authors.lastname: Abo
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000378:metabolism* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009205:Myocarditis / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000235:genetics* / Q000378:metabolism; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D012260:Ribonucleases / Q000737:chemistry / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D016207:Cytokines; D007375:Interleukin-1; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D054353:Perforin; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D012260:Ribonucleases