Interleukin-18 expression and the response to treatment in patients with psoriasis

Introduction

The aim of the study was to demonstrate Interleukin-18 (IL-18) expression in keratinocytes from psoriatic lesions in comparison to keratinocytes from uninvolved skin and to study the change of expression after therapeutic interventions.

Material and methods

This study included 16 patients of different clinical subtypes of psoriasis. IL-18 gene expression analysis was performed using real-time quantitative PCR. Three biopsies were obtained from each patient. Two were taken from the lesional psoriatic skin and from uninvolved skin before starting treatment. A third lesional skin biopsy was taken at the end of two months'' treatment course. The treatment was in the form of topical steroids or oral systemic methotrexate.

Results

Of all 16 studied patients significantly increased IL-18 expression was noted in keratinocytes from psoriatic lesions before and after treatment when compared to keratinocytes from uninvolved skin (P = 0.001 and 0.002 respectively). The IL-18 expression in the skin lesions after treatment was significantly lower than lesional skin before treatment (P = 0.023). In psoriatic skin lesions of all studied patients IL-18 expression was significantly correlated with disease duration (r = 0.40 and P = 0.01) and clinical severity of psoriasis (r = 0.72 and P = 0.001).

Conclusions

Increased IL-18 expression in keratinocytes from psoriatic lesions of our patients and its correlation with disease duration and severity supported the concept which views psoriasis as a T-cell-mediated autoimmune disease. This could establish therapeutic and preventive approaches for psoriasis that ultimately lead to improved outcomes for patients.     

A coagulation factor VII deficiency protects against acute inflammatory responses in mice

Upregulation of the activated Factor VII (FVIIa)/Tissue Factor complex, downregulation of natural anticoagulation pathways, and inhibition of fibrinolysis, are major contributors to coagulopathies associated with acute inflammation. Provision of FVIIa, and consequent downstream coagulation-related proteases, also stimulates further inflammatory changes, which can result in disseminated intravascular coagulation. Thus, the potential protective effects in vivo of a genetic-based reduction in FVII levels have been investigated in a murine model of acute inflammation, namely lipopolysaccharide (LPS)-induced lethal endotoxaemia. Mice with a total FVII deficiency do not survive the neonatal period. Therefore mice expressing low levels of FVII (FVII(tTA/tTA)), producing sufficient amounts of FVII for survival (approximately 5% of wild-type (WT) FVII), were employed to investigate in vivo pathways involved in the crosstalk between coagulation, inflammation, and survival, consequent to administration of a lethal dose of LPS. The FVII(tTA/tTA) mice presented with reduced mortality, coagulation, and inflammatory responses in comparison with similarly treated WT mice after administration of LPS. The attenuated inflammatory responses in FVII(tTA/tTA) mice were associated with downregulation of Egr-1 signalling. Administration, in vivo, of specific inhibitors of FXa and thrombin demonstrated that the inflammatory responses were unaltered in WT mice, but further reduced in FVII(tTA/tTA) mice. Therefore, a FVII deficiency enhances survival from lethal endotoxaemia both through attenuation of inflammatory responses that result directly from reduced FVIIa levels, and, indirectly, from downregulation of coagulation proteases downstream of the FVII-dependent cascade.     

Altered Immune Phenotype in Peripheral Blood Cells of Patients with Scleroderma‐Associated Pulmonary Hypertension

Pulmonary arterial hypertension is a common and fatal complication of scleroderma that may involve inflammatory and autoimmune mechanisms. Alterations in the gene expression of peripheral blood mononuclear cells have been previously described in patients with pulmonary arterial hypertension. Our goal is to identify differentially expressed genes in peripheral blood mononuclear cells in scleroderma patients with and without pulmonary hypertension as biomarkers of disease.Gene expression analysis was performed on a Microarray Cohort of scleroderma patients with (n= 10) and without (n= 10) pulmonary hypertension. Differentially expressed genes were confirmed in the Microarray Cohort and validated in a Validation Cohort of scleroderma patients with (n= 15) and without (n= 19) pulmonary hypertension by RT‐qPCR. We identified inflammatory and immune‐related genes including interleukin‐7 receptor (IL‐7R) and chemokine receptor 7 as differentially expressed in patients with scleroderma‐associated pulmonary hypertension. Flow cytometry confirmed decreased expression of IL‐7R on circulating CD4+ T‐cells from scleroderma patients with pulmonary hypertension.Differences exist in the expression of inflammatory and immune‐related genes in peripheral blood cells from patients with scleroderma‐related pulmonary hypertension compared to those with normal pulmonary artery pressures. These findings may have implications as biomarkers to screen at‐risk populations for early diagnosis and provide insight into mechanisms of scleroderma‐related pulmonary hypertension. Clin Trans Sci 2010; Volume 3: 210–218     

骨性关节炎患者退变软骨及滑膜组织中细胞因子的表达

背景：骨性关节炎的炎症反应是由软骨细胞、滑膜组织分泌的细胞因子所介导的。关节软骨和滑膜组织内含有多种细胞因子,在关节软骨的损伤修复中起着重要的调节作用。 目的：分析软骨细胞、滑膜组织分泌的细胞因子与骨性关节炎发病的关系及影响。 方法：由第一作者应用计算机检索万方数据库(www.wanfangdata.com.cn),PubMed数据库(www.ncbi.nlm.nih.guv/pubmed)检索时间：2005至2010年。检索词为“骨性关节炎,退变,软骨组织,细胞因子”。计算机初检得到146篇文献,阅读标题和摘要进行初筛,排除因研究目的与此文无关的86篇,内容重复性的研究40篇,保留21篇骨性关节炎患者退变软骨及滑膜组织中各种细胞因子作用及影响的相关文献作进一步分析。 结果与结论：细胞因子主要是指活化的免疫细胞和某些基质细胞分泌的一类非特异调节免疫应答和介导炎症反应的小分子蛋白质,包括由淋巴细胞产生的淋巴因子,单核巨噬细胞产生的单核因子及其他细胞因子等。关节滑膜细胞分泌的细胞因子可部分解释骨性关节炎的病理过程,在炎症关节中起着重要的作用。虽然越来越多的学者重视到滑膜细胞、软骨细胞分泌细胞因子的作用,但主要是研究外源性细胞因子对软骨细胞或滑膜细胞的影响,而其内源性细胞因子在骨性关节炎发病中的作用却未广泛开展研究。     

骨髓间充质干细胞对再生障碍性贫血患者T细胞的免疫抑制

背景：骨髓间充质干细胞对再生障碍性贫血患者T细胞增殖的影响国内报道较少,而骨髓间充质干细胞是否通过抑制T细胞增殖实现对再生障碍性贫血患者的免疫调节目前尚无定论。 目的：观察人骨髓间充质干细胞对再生障碍性贫血患者T细胞的免疫调节作用。 方法：体外分离培养、扩增人骨髓间充质干细胞并通过形态学特征以及流式细胞术进行表面标志鉴定,将骨髓间充质干细胞分别与正常人和再生障碍性贫血患者外周血提取的T淋巴细胞共培养7 d。应用ELISA法检测各培养上清液中T淋巴细胞分泌的白细胞介素2、γ-干扰素、白细胞介素4及白细胞介素10水平。 结果与结论：再生障碍性贫血组患者培养上清液中T淋巴细胞分泌的白细胞介素2、γ-干扰素水平明显高于正常人(P < 0.05),白细胞介素4、白细胞介素10低于正常人(P < 0.05)。骨髓间充质干细胞可下调白细胞介素2、γ-干扰素表达,同时上调白细胞介素4、白细胞介素10表达,从而调节再生障碍性贫血患者的免疫紊乱。     

抗炎症因子与类风湿性关节炎关系的研究进展

摘要： 类风湿性关节炎 （RA） 是一种慢性炎症性疾病, 疾病晚期可出现关节畸形和功能障碍, 严重危害人类健康。抗炎症因子 （AIC） 作为一种保护性因子, 和促炎症因子 （PIC） 共同在 RA 的发病和进展中发挥重要作用。RA 中 AIC 水平降低, PIC 水平升高, 全身和局部炎症反应加重, 关节软骨和软骨下骨破坏加速, 促进 RA 进一步进展的理念已经被广大学者接受, 以 AIC 为靶点的新一代 RA 生物学治疗方兴未艾。因此深入了解各种 AIC 在 RA 发病中的作用具有重要意义。本文从 AIC 与 RA 的关系和作用机制入手, 对该领域的研究进展进行综述, 为 RA 的临床诊治提供新的思路。     

Influence of training load on upper respiratory tract infection incidence and antigen‐stimulated cytokine production

This study examined the effect of training load on upper respiratory tract infection (URTI) incidence in men and women engaged in endurance‐based physical activity during winter and sought to establish if there are training‐associated differences in immune function related to patterns of illness. Seventy‐five individuals provided resting blood and saliva samples for determination of markers of systemic immunity. Weekly training and illness logs were kept for the following 4 months. Comparisons were made between subjects (n = 25) who reported that they exercised 3–6 h/week (LOW), 7–10 h/week (MED) or ≥ 11 h/week (HIGH). The HIGH and MED groups had more URTI episodes than the LOW group (2.4 ± 2.8 and 2.6 ± 2.2 vs 1.0 ± 1.6, respectively: P < 0.05). The HIGH group had approximately threefold higher interleukin (IL)‐2, IL‐4 and IL‐10 production (all P < 0.05) by antigen‐stimulated whole blood culture than the LOW group and the MED group had twofold higher IL‐10 production than the LOW group (P < 0.05). Other immune variables were not influenced by training load. It is concluded that high levels of physical activity are associated with increased risk of URTI and this may be related to an elevated anti‐inflammatory cytokine response to antigen challenge.