Laboratory of Dermatology and Immunodeficiencies (LIM-56), Department of Dermatology, Medical School of the University of São Paulo, São Paulo, Brazil.
Clin Exp Immunol. 2011 Nov;166(2):291-8. doi: 10.1111/j.1365-2249.2011.04473.x.
Immunological dysfunction has been described to occur in chronic idiopathic urticaria (CIU), most notably in association with an inflammatory process. Some pharmacological agents as statins--drugs used in hypercholesterolaemia--display a broad effect on the immune response and thus should be tested in vitro in CIU. Our main objectives were to evaluate the effects of statins on the innate and adaptive immune response in CIU. Simvastatin or lovastatin have markedly inhibited the peripheral blood mononuclear cells (PBMC) proliferative response induced by T and B cell mitogens, superantigen or recall antigen. Simvastatin arrested phytohaemaglutinin (PHA)-induced T cells at the G0/G1 phase, inhibiting T helper type 1 (Th1), Th2, interleukin (IL)-10 and IL-17A cytokine secretion in both patients and healthy control groups. Up-regulation of suppressor of cytokine signalling 3 (SOCS3) mRNA expression in PHA-stimulated PBMCs from CIU patients was not modified by simvastatin, in contrast to the enhancing effect in the control group. Statin exhibited a less efficient inhibition effect on cytokine production [IL-6 and macrophage inflammatory protein (MIP)-1α] induced by Toll-like receptor (TLR)-4, to which a statin preincubation step was required. Furthermore, statin did not affect the tumour necrosis factor (TNF)-α secretion by lipopolysaccharide (LPS)-stimulated PBMC or CD14+ cells in CIU patients. In addition, LPS-activated PBMC from CIU patients showed impaired indoleamine 2,3-dioxygenase (IDO) mRNA expression compared to healthy control, which remained at decreased levels with statin treatment. Statins exhibited a marked down-regulatory effect in T cell functions, but were not able to control TLR-4 activation in CIU patients. The unbalanced regulatory SOCS3 and IDO expressions in CIU may contribute to the pathogenesis of the disease.
免疫功能障碍已被描述为发生在慢性特发性荨麻疹（CIU）中，尤其是与炎症过程有关。一些药理学药物，如他汀类药物 - 用于高胆固醇血症的药物 - 对免疫反应具有广泛的影响，因此应在 CIU 中进行体外测试。我们的主要目标是评估他汀类药物对 CIU 中先天和适应性免疫反应的影响。辛伐他汀或洛伐他汀显着抑制了由 T 和 B 细胞有丝分裂原、超抗原或回忆抗原诱导的外周血单核细胞（PBMC）增殖反应。辛伐他汀使植物血凝素（PHA）诱导的 T 细胞停滞在 G0/G1 期，抑制 Th1、Th2、白细胞介素（IL）-10 和 IL-17A 细胞因子在患者和健康对照组中的分泌。与对照组增强作用相反，PHA 刺激的 CIU 患者 PBMC 中的细胞因子信号转导抑制因子 3（SOCS3）mRNA 表达的上调不受辛伐他汀调节。他汀类药物对 Toll 样受体（TLR）-4 诱导的细胞因子产生（IL-6 和巨噬细胞炎性蛋白（MIP）-1α）的抑制作用效率较低，需要他汀类药物预孵育步骤。此外，他汀类药物对 LPS 刺激的 CIU 患者 PBMC 或 CD14+细胞中 TNF-α 的分泌没有影响。此外，与健康对照组相比，CIU 患者的 LPS 激活的 PBMC 中吲哚胺 2,3-双加氧酶（IDO）mRNA 表达受损，而在用他汀类药物治疗后仍保持较低水平。他汀类药物对 T 细胞功能具有明显的下调作用，但不能控制 CIU 患者 TLR-4 的激活。CIU 中不平衡的调节 SOCS3 和 IDO 表达可能有助于疾病的发病机制。
