Influence of SNPs in cytokine-related genes on the severity of food allergy and atopic eczema in children

Although many single nucleotide polymorphism (SNP) studies have reported an association of atopy, allergic diseases and total serum immunoglobulin E (IgE) levels, almost all of these studies sought risk factors for the onset of these allergic diseases. Furthermore, many studies have analyzed a single gene and hardly any have analyzed environmental factors. In these analyses, the results could be masked and the effects of other genes and environmental factors may be decreased. Here, we described the correlation between four genes [interleukin (IL)-4 (C-590T), IL-4 receptor (A1652G), FCER1B (G6842A) and STAT6 (G2964A)] in connection with IgE production; the role of IL-10 (C-627A) as a regulatory cytokine of allergy; and the severity of food allergy (FA) and atopic eczema (AE) in 220 Japanese allergic children. In addition to these SNPs, environmental factors, i.e., patient's attitude, indoor environment, and so on, were also investigated in this study. Our study was retrospective, and the correlation was analyzed by our defined clinical scores divided into three terms: worst symptoms, recent symptoms and general amelioration at the most recent examination during the disease course. Our results indicated that IL-10 AA, the genotype with lower IL-10 production, is associated with higher IgE levels in the serum (p < 0.0001, estimate; 0.912). Marginal liver abnormalities were observed in the subject group with both FA and AE (p < 0.1191, estimate; 0.1490). Our defined clinical scores enabled evaluation of various aspects of disease severity. Based on the scores, while no single SNP selected in this study determined severity, the combination of the SNP with laboratory data and environmental factors appeared to determine severity.     

TGF-β and IL-17 serum levels and specific immunotherapy

Two new T cell subsets may be involved in allergic rhinitis (AR) pathogenesis: Th17 and T regulatory cells, mainly producing IL-17 and TGF-β respectively. Successful Sublingual Immunotherapy (SLIT) induces relevant immunological changes, thus the aim of this study was to evaluate serum IL-17 and TGF-β levels in AR patients treated with SLIT for 2 years. Patients' blood samples were collected before initiating SLIT (baseline), three months after the end of the first pre-seasonal SLIT course, and at the end of the second pre-seasonal course. IL-17 was detectable only in the most severe allergic patients. SLIT significantly induced an increase in serum TGF-β levels. There was moreover a significant relationship between TGF-β and symptom severity and drug use at the end of the study. Therefore, this study provides clinically relevant evidence that two pre-seasonal SLIT courses may significantly affect serum TGF-β levels.     

正常人外周血淋巴细胞 IL—2受体免疫放射测定

采用~(125)I 标记小鼠抗人IL—2受体(P55)的抗Tac(CD_(25))单克隆抗体,成功地建立了人IL—2受体的免疫放射分析法,动态观察了人外周血淋巴细胞经PHA 刺激24、48和72h 后IL—2受体表达的时间曲线,通过Scatchard 作图分析表明~(125)I—抗Tac 单克隆抗体与PHA 活化的上述三个时间点的T 淋巴细胞的最大结合容量(B_(max))分别为43000位点/细胞、54000位点/细胞和61000位点/细胞。本研究为临床IL—2受体检测提供一种简便的免疫放射测定法。     

Gingival crevicular fluid IL-8: correlation with local IL-1β levels and patient estrogen status

Gingival crevicular fluid (GCF) IL-8 and IL-1,1β levels were determined by sandwich enzyme-linked immunosorbent assays. Associations between IL-8 and IL-1β GCF levels, and between these cytokines and patient estrogen status were evaluated. IL-8 and IL-1β were detected more frequently and in higher amounts/30 s GCF sample in estrogen-deficient patients than in estrogensufficient patients. IL-8 and IL-1β GCF levels were significantly correlated. These lindings suggest that GCF IL-8 levels are associated with patient estrogen status and local IL-1β concentrations.     

IFN-γ,IL-4水平对血透患者外周血PBLC Fas,Bcl-2表达的影响

目的研究IFN-γ,IL-4水平对血透患者外周血淋巴细胞(PBLC)凋亡调控蛋白Fas,Bcl-2表达的影响.方法采用流式细胞术的间接免疫荧光素标记法和双抗体夹心ELISA法,分别检测30例HD患者PBLC Fas,Bcl-2的表达水平和血清IFN-γ,IL-4水平.结果H-D患者血清IFN-γ水平明显低于健康对照组,IL-4浓度显著高于对照组(P均＜0.01);其外周血PBLC的Fas表达水平明显高于健康对照组,而Bcl-2水平则明显低于健康对照组(P均＜0.01).经相关分析发现:Fas表达水平与血清IFN-γ水平呈负相关,而与血清IL-4水平呈正相关(P均＜0.01);Bcl-2表达水平与血清IFN-γ水平呈正相关,而与血清IL-4水平呈负相关(P均＜0.01).结论HD患者PBLC存在异常凋亡现象;并与Th1型细胞因子分泌低下,以及TTh2型细胞因子分泌增加之间有一定的相关性,上述改变可能在HD患者的免疫功能紊乱中起着重要作用.     

Possible role of IL-2 deficiency for hypogammaglobulinaemia in patients with common variable immunodeficiency.

Common variable immunodeficiency (CVID) patients are unable to produce specific immunoglobulins after antigen contact in vivo. The aim of this study was to investigate whether in some cases of CVID a decreased de novo synthesis of IL-2 might be the cause of immunodeficiency and whether this deficiency can be corrected by IL-2 supplementation in vitro. Mononuclear cells from 17 CVID patients and from 10 healthy controls were cultured with monoclonal anti-CD3 antibody OKT3, pokeweed mitogen (PWM) or tetanus toxoid (TT) to stimulate IL-2 synthesis. In parallel, in vitro IgG and IgM synthesis was stimulated with Staphylococcus aureus Cowan I (SAC), PWM or TT in the presence or absence of IL-2. While lymphocytes of 11 out of 17 patients produced low to normal amounts of IL-2 upon stimulation with anti-CD3, only three patients showed low IL-2 production in response to PWM and five in response to TT. Regarding immunoglobulin synthesis in vitro, five patients completely failed to produce IgM or IgG upon stimulation with PWM, SAC or TT irrespective of the addition of IL-2. By contrast, four patients did not show any defect in vitro and synthesized normal amounts of IgM and IgG with any of the three stimuli. Finally, eight patients could be reconstituted for PWM-, SAC- and TT-induced IgM and/or IgG synthesis in vitro, by adding IL-2 to the culture system. This enhancing effect of IL-2 could be blocked by adding anti-IL-2 receptor antibodies to the cultures. Our findings indicate that a defective IL-2 synthesis after antigen stimulation may be one reason for the impaired immunoglobulin production in some cases of CVID.     

The effect of anti-IL-4 monoclonal antibody, rapamycin and interferon-γ on airway hyperreactivity to acetylcholine in mice

Background The role of IgE in airway hyperreaetivity is obscure. Objective In order to clarify the role of IgE in airway hyperreactivity, we investigated the effect of anti-IL-4 monoclonal antibody, rapamycin and interferon-γ on the antigen-induced IgE response, airway eosinophilia and hyperreactivity in mice. Methods Mice were immunized with an antigen (ovalbumin; OA) at intervals of 12 days. OA was inhaled 10 days after the secondary immunization. Twenty-four hours after the last inhalation, airway reactivity to acetylcholine was measured and bronchoalveolar lavage fluid (BALF) was obtained. Results Three inhalations of antigen caused an increase in the number of eosinophils in bronchoalveolar lavage fluid (BALF) and in airway hyperreactivity to acetylcholine with a significant elevation of serum IgE level. Anti-IL-4 at a dose of 1000 μg/animal and rapamycin at doses between 0.1 and 1 mg/kg inhibited the IgE production, but did not affect the airway eosinophilia or hyperreactivity to acetylcholine. In contrast, IFN-γ clearly inhibited the antigen-induced airway eosinophilia and hyperreactivity, but did not affect the IgE antibody production. Conclusion These results suggest that the inhibition of IgE production does not suppress the onset of airway hyperreactivity and eosinophilia in mice, and that IFN-γ inhibits the antigen-induced airway hyperreactivity, probably due to the inhibition of airway eosinophilia.     

静脉用丙种球蛋白治疗新生儿重症感染对细胞免疫功能的影响

应用静脉注丙球(IVIG),配合抗生素(An)治疗重症感染新生儿12例,在观察疗效及不良反应的同时,通过检测患儿治疗前后T细胞亚群及白细胞介素Ⅱ(IL-2)产生水平的变化,观察IVIG对细胞免疫功能的影响。结果显示:患儿CD_3~+、CD_4~+、CD_8~+细胞及IL-2产生水平均明显低于正常同龄新生儿。经IVIG+An及单用An治疗后,T细胞各亚群及IL-2水平均明显增高。IVIG组与An组比较,诒疗后IVIG组CD_4~+细胞明显高于An组,IL-2水平也较An组为高,但无统计学意义。疗效观察,中毒症状及原发病体征好转消失时间IVIG组较An组明显缩短。本文还就IVIG对细胞免疫功能影响的可能机制进行了讨论。