Kimmel Martin, Alscher Dominik Mark, Dunst Robert, Braun Niko, Machleidt Christoph, Kiefer Thomas, Stülten Christina, van der Kuip Heiko, Pauli-Magnus Christiane, Raub Ulrich, Kuhlmann Ulrich, Mettang Thomas
Division of General Internal Medicine and Nephrology, Department of Internal Medicine, Robert-Bosch Hospital, Germany.
Nephrol Dial Transplant. 2006 Mar;21(3):749-55. doi: 10.1093/ndt/gfi204. Epub 2005 Oct 25.
Uraemic pruritus (UP) is still one of the most vexing and disabling symptoms in chronic renal failure. The pathogenesis of UP is obscure and effective therapeutic strategies are elusive. Deduced from partial successful treatment modalities, there is evidence that an alteration of the immune system with a pro-inflammatory pattern along with a deranged T-helper-cell differentiation may be involved in the pathogenesis of UP. We, therefore, investigated whether UP is related to an augmented Th1-differentiation as measured by determination of intracytoplasmatic (i.c.) cytokines and expression of chemokine receptors. Additionally, pro-inflammatory cytokines were determined in serum.
In a multicentre study, 171 patients on haemodialysis (HD) were screened for UP. Finally, 13 HD patients with and 13 HD patients without UP, as well as 15 healthy controls were enrolled in the study. Peripheral blood mononuclear cells were isolated and the proportion of Th1- and Th2-cells was determined by flow cytometry. The expression of chemokine receptors on CD4 cells (CXCR3 preferentially on Th1 and CCR4 on Th2) and i.c. cytokines (IFNgamma for Th1 and IL4 for Th2) were measured after in vitro stimulation. Serum cytokine levels (IL6 and TNFalpha) and CRP were measured by ELISA.
Compared to HD patients without UP, those complaining of UP showed a significantly enhanced proportion of Th1-cells as measured by both techniques. Additionally, serum CRP and IL6 levels were significantly higher in HD patients with UP, compared to HD patients without UP.
These results point to a central role of inflammation in the pathogenesis of UP in HD patients.
尿毒症瘙痒（UP）仍是慢性肾衰竭中最令人烦恼且使人功能受限的症状之一。UP的发病机制尚不明确，有效的治疗策略也难以捉摸。从部分成功的治疗方式推断，有证据表明免疫系统的改变伴有促炎模式以及T辅助细胞分化紊乱可能参与了UP的发病机制。因此，我们研究了UP是否与通过测定胞质内（i.c.）细胞因子和趋化因子受体表达所衡量的Th1分化增强有关。此外，还测定了血清中的促炎细胞因子。
在一项多中心研究中，对171例血液透析（HD）患者进行了UP筛查。最终，13例有UP的HD患者、13例无UP的HD患者以及15名健康对照者被纳入研究。分离外周血单个核细胞，通过流式细胞术测定Th1和Th2细胞的比例。体外刺激后，测量CD4细胞上趋化因子受体（CXCR3主要在Th1上，CCR4在Th2上）的表达以及胞质内细胞因子（Th1的IFNγ和Th2的IL4）。通过ELISA测定血清细胞因子水平（IL6和TNFα）和CRP。
与无UP的HD患者相比，主诉有UP的患者通过两种技术测量均显示Th1细胞比例显著增加。此外，有UP的HD患者血清CRP和IL6水平显著高于无UP的HD患者。
这些结果表明炎症在HD患者UP的发病机制中起核心作用。
