School of Nursing, University of South China, Hengyang, Hunan 421001, China.
Chin Med J (Engl). 2012 Jan;125(1):50-5.
Macrophage migration inhibitory factor (MIF) is an upstream regulator in immune and inflammatory responses. However, its role in viral myocarditis remains unknown. In this study, we investigated the role of the MIF in coxsackievirus B3 (CVB3)-induced myocarditis.
Mice were randomized into two groups receiving either Eagle's minimal essential medium (EMEM, control group) or virus solution (infected group). Subsets of mice in the infected group were sacrificed on days 3, 7, 14 and 28 after inoculation. Expression of MIF was detected using an enzyme-linked immunosorbent assay (ELISA), reverse transcription polymerase chain reaction and immunohistochemistry. A neutralizing antibody (Ab) to MIF was injected intraperitoneally from day 0 to 7 after inoculation. Disease severity was estimated by histopathology of the heart and by the heart weight to body weight ratio, and the interleukin-1β (IL-1β) and tumor necrosis factor α (TNF-α) in the myocardium were measured by ELISA on day 14.
The serum MIF concentration and expression levels of myocardial MIF mRNA and protein were significantly elevated in mice on days 7 and 14 post-infection. The survival rate was markedly higher and disease severity was obviously less in mice treated with anti-MIF Ab. Furthermore, MIF blockade significantly decreased the IL-1β and TNF-α in the myocarditic heart.
These results demonstrate that MIF is an important naturally occurring inflammatory cytokine in CVB3-induced myocarditis, and anti-MIF Ab may lessen the inflammatory response.
巨噬细胞移动抑制因子（MIF）是免疫和炎症反应的上游调节剂。然而，其在病毒性心肌炎中的作用尚不清楚。在这项研究中，我们研究了 MIF 在柯萨奇病毒 B3（CVB3）诱导的心肌炎中的作用。
将小鼠随机分为两组，分别接受 Eagle's 最小必需培养基（EMEM，对照组）或病毒溶液（感染组）。感染组的部分小鼠在接种后第 3、7、14 和 28 天被处死。使用酶联免疫吸附试验（ELISA）、逆转录聚合酶链反应和免疫组织化学检测 MIF 的表达。从接种后第 0 天到第 7 天，通过腹腔内注射 MIF 的中和抗体（Ab）。通过心脏组织病理学和心脏重量与体重比评估疾病严重程度，并在第 14 天通过 ELISA 测量心肌中的白细胞介素 1β（IL-1β）和肿瘤坏死因子 α（TNF-α）。
感染后第 7 天和第 14 天，小鼠血清 MIF 浓度以及心肌 MIF mRNA 和蛋白表达水平显著升高。用抗 MIF Ab 治疗的小鼠存活率明显更高，疾病严重程度明显减轻。此外，MIF 阻断显著降低了心肌炎心脏中的 IL-1β和 TNF-α。
这些结果表明，MIF 是 CVB3 诱导的心肌炎中一种重要的天然炎症细胞因子，抗 MIF Ab 可能减轻炎症反应。
