Hod Eldad A, Cadwell Chantel M, Liepkalns Justine S, Zimring James C, Sokol Set A, Schirmer David A, Jhang Jeffrey, Spitalnik Steven L
Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10023, USA.
Blood. 2008 Aug 1;112(3):891-4. doi: 10.1182/blood-2008-01-132092. Epub 2008 May 15.
Cytokines are hypothesized to play a central role in the pathophysiology of IgG-mediated hemolytic transfusion reactions (HTRs), and deeper understanding is required for improving therapy for these events. After establishing well-defined mouse models of HTRs, we tested whether cytokines were involved. Red blood cells (RBCs) from human glycophorin A transgenic (hGPA-Tg) or wild-type (WT) mice were transfused into non-Tg recipients passively immunized with monoclonal antibodies (Mabs). Only transfusions of incompatible RBCs induced IgG-mediated HTRs, exemplified by rapid clearance and hemoglobinuria. Very high plasma levels of monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6), and lower levels of tumor necrosis factor-alpha (TNF-alpha), were induced after incompatible transfusion. No significant changes in IL-10, IL-12, or interferon-gamma (IFN-gamma) levels were observed. The proinflammatory cytokines elaborated in this in vivo mouse model are also implicated in the systemic inflammatory response syndrome (SIRS) and confirm the hypothesis that cytokine storm occurs as a result of HTRs.
细胞因子被认为在IgG介导的溶血性输血反应（HTRs）的病理生理学中起核心作用，为改善这些事件的治疗方法，需要更深入的了解。在建立明确的HTRs小鼠模型后，我们测试了细胞因子是否参与其中。将来自人血型糖蛋白A转基因（hGPA-Tg）或野生型（WT）小鼠的红细胞（RBCs）输注到用单克隆抗体（Mabs）被动免疫的非转基因受体中。只有不相容红细胞的输注会诱导IgG介导的HTRs，表现为快速清除和血红蛋白尿。不相容输血后，血浆中单核细胞趋化蛋白-1（MCP-1）和白细胞介素-6（IL-6）水平非常高，而肿瘤坏死因子-α（TNF-α）水平较低。未观察到IL-10、IL-12或干扰素-γ（IFN-γ）水平有显著变化。在这个体内小鼠模型中产生的促炎细胞因子也与全身炎症反应综合征（SIRS）有关，并证实了细胞因子风暴是由HTRs引起的这一假设。
