Division of Clinical Immunology, Department of Internal Medicine, University of Genoa Medical School, 16132, Genoa, Italy.
J Clin Immunol. 2010 May;30(3):384-92. doi: 10.1007/s10875-009-9364-y. Epub 2010 Feb 2.
Numerous mechanisms have been proposed to explain the beneficial action of intravenous immune globulin (IVIG) in autoimmune and systemic inflammatory disorders; among others, they could decrease pro-inflammatory cytokine levels and also induce anti-inflammatory cytokines.
Ex vivo analysis of cells from ten IVIG recipients showed significant increase of IL-10 mRNA and intra-cellular IL-10 molecules in both leukotypes.
In vitro comparable results were obtained incubating CD8(+) T lymphocytes and neutrophils from healthy donors with IVIG. sHLA-I and/or sFasL immunodepletion abolished IL-10 modulation. Co-culture with contaminant-free IgM or MabThera did not exert any mRNA modulation. Finally, IgM or MabThera plus purified sHLA-I molecules enhanced IL-10-mRNA in both leukotypes to levels comparable to those obtained with IVIG incubation.
As IVIG infusion involves administration of soluble contaminants, these data consent to speculate that IVIG might modulate IL-10 via the immunomodulatory activities of sHLA-I contaminant molecules inducing transcriptional and post-transcriptional modulation of IL-10 in CD8(+) T lymphocytes and neutrophils.
许多机制被提出以解释静脉注射免疫球蛋白（IVIG）在自身免疫和系统性炎症性疾病中的有益作用；其中，它可以降低促炎细胞因子水平，并诱导抗炎细胞因子。
对十名 IVIG 接受者的细胞进行离体分析，结果显示白细胞类型中 IL-10 mRNA 和细胞内 IL-10 分子均显著增加。
体外实验中，用 IVIG 孵育健康供体的 CD8(+)T 淋巴细胞和中性粒细胞，也得到了相似的结果。sHLA-I 和/或 sFasL 免疫耗竭可消除 IL-10 的调节作用。与无污染物的 IgM 或 MabThera 共培养不会引起任何 mRNA 调节。最后，IgM 或 MabThera 加纯化的 sHLA-I 分子可增强两种白细胞类型中的 IL-10-mRNA，使其达到与 IVIG 孵育相当的水平。
由于 IVIG 输注涉及可溶性污染物的给药，这些数据提示 IVIG 可能通过免疫调节活性的 sHLA-I 污染物分子来调节 IL-10，诱导 CD8(+)T 淋巴细胞和中性粒细胞中 IL-10 的转录和转录后调节。
