Mahmoud F, Abul H, al-Seleh Q, Morgan G, Haines D, al-Ramly M, Burleson J, Kreutzer D
Department of Medical Laboratory Sciences, Faculty of Allied Health Sciences and Nursing, Kuwait University, Sulaibekhat, Kuwait.
J Dermatol. 1999 Jan;26(1):23-8. doi: 10.1111/j.1346-8138.1999.tb03504.x.
Most diseases exhibit characteristic profiles of cytokine expression, broadly subdivided into Th1, involving primarily cell-mediated responses, of which Interferon-gamma (INF-gamma), Interleukin-2 (IL-2) and Tumor Necrosis Factor-alpha (TNF-alpha) are hallmarks, and Th2 processes, which often involve activation of the humoral arm of the immune system, resulting in elevated levels of IL-4, IL-5 and IL-10. Psoriasis, a disorder characterized by disfiguring skin lesions and elevated levels of activated CD4+ T helper lymphocytes in both peripheral blood and lesional tissue, exhibits a profile of cytokine expression that includes high levels of TNF-alpha and IFN-gamma, with low IL-5 and IL-10, indicating that immunologically, the pathogenesis of the disease is Th1. In this study, we report the results of an investigation of peripheral blood mononuclear cell cytokine expression among Kuwaiti psoriasis patients; we demonstrated two patterns of IFN-gamma production which may suggest differing pathogeneses. Whole, haparinized blood was donated by 17 patients with active psoriasis and 11 healthy control subject. Mononuclear cells were isolated by density centrifugation and cultured for 3 days in the presence or absence of a mitogen (PHA). Supernatants were assayed for IFN-gamma (a Th1 marker) and IL-10 (a Th2 marker) by enzyme-linked immunoabsorption assay (ELISA). IFN-gamma expression by both PHA-stimulated and unstimulated cultures from psoriatics significantly exceeded that of controls (p < 0.001), whereas no significant differences in IL-10 expression were noted between psoriatic and control subjects. Stimulation indices (cytokine concentration in PHA-stimulated/unstimulated cultures, SI) for psoriatic subjects were significantly higher than those of controls for IFN-gamma (p = 0.000), but not for IL-10. Ratios of SI (SI IFN-gamma/SL IL-10) for the psoriatic subjects also were significantly greater for the psoriatic subjects than for the controls (p = 0.003). However, within the psoriatic group, eight patients failed to show the expected elevation of IFN-gamma/IL-10 ratio as a result of high unstimulated levels of IFN-gamma production. The divergence of IFN-gamma expression within the psoriatic group may indicate two different modes of T lymphocyte activation contributing to the pathogenesis of psoriasis in this study.
大多数疾病都表现出细胞因子表达的特征性模式，大致可分为Th1型，主要涉及细胞介导的反应，其中γ干扰素（INF-γ）、白细胞介素-2（IL-2）和肿瘤坏死因子-α（TNF-α）是其标志；以及Th2型过程，这通常涉及免疫系统体液分支的激活，导致IL-4、IL-5和IL-10水平升高。银屑病是一种以毁容性皮肤病变以及外周血和病变组织中活化的CD4+辅助性T淋巴细胞水平升高为特征的疾病，其细胞因子表达模式包括高水平的TNF-α和IFN-γ，而IL-5和IL-10水平较低，这表明在免疫学上，该疾病的发病机制为Th1型。在本研究中，我们报告了对科威特银屑病患者外周血单核细胞细胞因子表达的调查结果；我们发现了两种IFN-γ产生模式，这可能提示不同的发病机制。17例活动性银屑病患者和11名健康对照者捐献了全血并进行肝素化处理。通过密度离心分离单核细胞，并在有或无丝裂原（PHA）的情况下培养3天。通过酶联免疫吸附测定（ELISA）检测上清液中的IFN-γ（一种Th1标志物）和IL-10（一种Th2标志物）。银屑病患者经PHA刺激和未经刺激的培养物中IFN-γ的表达均显著超过对照组（p < 0.001），而银屑病患者和对照者之间IL-10表达未观察到显著差异。银屑病患者的刺激指数（PHA刺激培养物与未刺激培养物中细胞因子浓度之比，SI）在IFN-γ方面显著高于对照组（p = 0.000），但在IL-10方面并非如此。银屑病患者的SI比值（SI IFN-γ/SL IL-10）也显著高于对照组（p = 0.003）。然而，在银屑病患者组中，8例患者由于未刺激状态下IFN-γ产生水平较高，未表现出预期的IFN-γ/IL-10比值升高。银屑病患者组中IFN-γ表达的差异可能表明在本研究中T淋巴细胞激活的两种不同模式促成了银屑病的发病机制。
