Okura Y, Yamamoto T, Goto S, Inomata T, Hirono S, Hanawa H, Feng L, Wilson C B, Kihara I, Izumi T, Shibata A, Aizawa Y, Seki S, Abo T
Department of Immunology, Niigata University School of Medicine, Japan.
J Mol Cell Cardiol. 1997 Feb;29(2):491-502. doi: 10.1006/jmcc.1996.0293.
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.
采用核糖核酸酶保护分析法，以证明在大鼠实验性自身免疫性心肌炎（EAM）病程中，心肌中几种细胞因子以及诱导型一氧化氮合酶（iNOS）、组成型内皮一氧化氮合酶（cNOS）和穿孔素的mRNA表达情况。白细胞介素2（IL-2）出现在初始炎症期（第14天），在最大炎症期（第19天）消退，并在恢复期（第25天）消失。IL-3β、干扰素γ（INF-γ）和肿瘤坏死因子α（TNF-α）的mRNA仅在最大炎症期被检测到，此时iNOS也出现了几天。相比之下，IL-10 mRNA在最大炎症期之后被检测到，并持续到恢复期（第25 - 36天）。虽然在所有阶段都能检测到转化生长因子β1（TGF-β1），但其表达在最大炎症期明显增强，并在第36天左右逐渐降至基础水平。在疾病的任何阶段都未检测到穿孔素mRNA。除了巨噬细胞和CD4 T细胞外，在心肌中发现了大量中性粒细胞，尤其是在炎症高峰期。我们认为，抗原致敏的抗原呈递细胞或巨噬细胞与T细胞（Th1）相互作用产生IL-2及随后的IFN-γ，这进一步激活心肌中的巨噬细胞。因此，TNF-α和iNOS可能对心肌造成组织损伤。也有人认为，TGF-β1和一种代表性的Th2细胞因子IL-10有助于抑制炎症。这些发现表明，Th1和Th2细胞因子在EAM的不同阶段产生，并调节炎症及EAM的病程。
