Adamantiades-Behçet’s disease: interleukin-8 is increased in serum of patients with active oral and neurological manifestations and is secreted by small vessel endothelial cells

The serum levels of several cytokines were determined in 94 patients with Adamantiades-Beh?et's disease (ABD), aged 36.1+/-11.0 years, during the active stage (n = 75) and the inactive stage (n = 19) of the disease. A group of 75 healthy individuals matched for age and sex served as controls. Cytokine levels were determined using commercially available ELISA kits. Of the 75 patients with active disease and 19 with inactive disease, 38 (51%) and 4 (21%), respectively, and 23 healthy controls (31%) were found to have detectable levels of interleukin 8 (IL-8) in their serum (P < 0.05). Also, increased IL-8 serum levels were found in patients with active disease (median 12 pg/ml, P = 0.010) compared to patients with inactive disease (< or = 10 pg/ml) and to healthy controls (< or = 10 pg/ml). In particular, patients with oral aphthous ulcers (n = 51, 34 pg/ml) and neurological features (n = 4, 71 pg/ml) exhibited increased IL-8 levels. In contrast, there was no correlation between disease activity and the serum levels of IL-1alpha, IL-1beta, tumor necrosis factor alpha (TNF-alpha), soluble intercellular adhesion molecule-1 or basic fibroblast growth factor (bFGF). In a second set of experiments, the involvement of dermal microvascular endothelial cells in IL-8 secretion was investigated. Immortalized human dermal microvascular endothelial cells (HMEC-1 cells) were maintained for 4 h in vitro with serum from 18 ABD patients or with IL-1beta, a known stimulator of IL-8 synthesis, TNF-alpha or their combination at five- to tenfold higher concentrations than those found in the serum of ABD patients. Increased IL-8 secretion was found after incubation with ABD patients' serum (median 20 pg/ml), but IL-1beta, TNF-alpha and IL-1beta + TNF-alpha failed to induce IL-8 secretion by HMEC-1 cells (< or = 1-1.2 pg/ml) in biologically relevant concentrations. Our study showed increased IL-8 serum levels in ABD patients with active oral and neurological manifestations. Human microvascular endothelial cells may, at least partially, be responsible for the enhanced IL-8 secretion in the active stage of the disease.     

Serum cytokine levels in atopic dermatitis

Elevated IgE responses and eosinophilia observed in patients with atopic dermatitis (AD) may reflect increased responses of type 2 T-helper (Th2) cytokines with a concomitant decrease in interferon-gamma (IFN-gamma) production. However, the cross-regulation of Th1/Th2 derivation and function in AD patients are incompletely characterized. Therefore, we investigated serum levels of several cytokines [interleukin (IL)-18, IL-12, IL-10, IL-2 and IFN-gamma] in patients with AD to assess their possible relationships to the severity of disease. Serum IL-18 levels in AD patients were significantly higher than those in healthy controls [207 pg/mL; 95% confidence interval (CI), 172-242 pg/mL vs. 144 pg/mL; 95% CI, 116-178 pg/mL; P = 0.026]. Those IL-18 levels significantly correlated with eosinophil counts and serum soluble IL-2 receptor (sIL-2R) levels, and showed a tendency to correlate with clinical severity scores and serum IgE levels. IL-2 levels showed a significantly inverse correlation with serum IgE levels, and IL-12 levels clearly correlated with IL-10 levels. These results suggest the value of serum IL-18 levels as a parameter of AD activity and may support a possible role for IL-18 in the pathogenesis of AD. The inverse correlation between IgE levels and IL-2 levels suggests that IgE production may be inhibited by IL-2 in patients with AD. Furthermore, the correlation of IL-12 levels with IL-10 levels may support the previous reports that show the induction of IL-10 production by human natural killer cells and/or T cells stimulated with IL-12 in vitro.     

Oxidative stress in patients with Behcet's disease: I correlation with severity and clinical parameters

The study was designed to investigate the possible correlation between some oxidative stress parameters in Behcet's disease and the clinical manifestations of the disease as well as the possible correlation with the disease severity. Seventy-six patients diagnosed according to the International Study Group criteria for Behcet's disease were included in the study. Sixty patients had mild-to-moderate disease and 16 patients had severe disease. Sixty matched control subjects were also included. After a full history and examination from each subject, 10 mL blood was drawn from each for analysis. Serum malondialdehyde, glutathione, ceruloplasmin, copper and zinc levels were determined. Patients with Behcet's disease showed increased levels of serum malondialdehyde and copper while glutathione and zinc levels were decreased. Comparison between these parameters in patients with mild-to-moderate disease with those with severe disease showed only that serum zinc levels were lower in severe Behcet's disease. Serum malondialdehyde levels were found to be significantly positively correlated with oral ulcer size, duration and frequency. Glutathione levels were found to be inversely correlated with the clinical manifestation index and all oral ulcer parameters. Zinc levels were found to be inversely correlated with the clinical manifestation index and pathergy test positivity grades. Copper levels were found to be positively correlated with oral ulcer number. Although the parameters of oxidative stress did not show correlation with disease severity, they were correlated with the disease manifestations. This points out the importance of oxidative stress in Behcet's disease.     

特异性免疫治疗对慢性荨麻疹患者血清白介素-18和白介素-10水平的影响

目的:检测慢性荨麻疹患者特异性免疫治疗(specific immunotherapy SIT)前后Th1型细胞因子白介素-18(IL-18)和Th2型细胞因子白介素-10(IL-10)血清水平。方法:ELISA法检测30例变应原皮肤试验阳性荨麻疹患者特异性免疫治疗前后及20例正常人血清IL-18和IL-10水平。结果:慢性荨麻疹患者SIT前IL-18水平低于正常人(P<0.05),SIT后升高(P<0.05);SIT前IL-10水平高于正常人(P<0.05),SIT后下降(P<0.05)。结论:变应原皮试阳性荨麻疹患者IL-18降低,IL-10升高,Th1/Th2失衡在慢性荨麻疹的发病中具有重要作用。特异性免疫治疗可能通过调节Th1/Th2平衡而发挥治疗作用。     

Serum concentration of IL-18 correlates with disease extent in young children with atopic dermatitis

Interleukin (IL)-18 is a pleiotropic cytokine that plays an important role in both type 1 (Th1) and type 2 (Th2) helper T lymphocyte-mediated immunity. Previous studies have suggested that IL-18 may be an inflammatory marker for atopic dermatitis (AD). The purpose of our study was to test whether the serum concentration of IL-18 is a useful inflammatory marker for assessing AD severity in young children. Nineteen AD patients with a median age of 2.2 years (interquartile range 0.7-4.6 years) were recruited. The severity of AD was clinically determined using the Scoring Atopic Dermatitis (SCORAD) index. Their SCORAD score was 23.9 (range 18.6-34.8). Serum IL-18 levels were determined by sandwich enzyme immunoassay. The median serum concentration of IL-18 was 394 pg/ml (interquartile range 204-612 pg/ml). Serum IL-18 levels correlated with SCORAD scores (r = 0.502, p = 0.029) and their extent component (r = 0.633, p = 0.004). When compared with mild disease with low SCORAD scores, the serum concentration in moderate to severe disease was significantly higher (p = 0.014). We concluded that serum IL-18 concentration is elevated in young children with AD. It may be a useful inflammatory marker that correlates with the extent component of AD in particular, and differentiates mild disease from more severe disease when used for assessing AD severity in young children.     

Decreased Interleukin-7 and transforming growth factor-beta1 levels in blister fluids as compared to the respective serum levels in patients with bullous pemphigoid: Opposite behavior of TNF-alpha, Interleukin-4 and Interleukin-10

Abstract: This study analyzes both the blister fluid (BF) and serum levels of IL-7 and TGF-beta₁ in samples from 18 patients affected with bullous pemphigoid (BP). These cytokines clearly present lower concentrations ( P <0.001) in BFs than in the sera (1/20 and 1/2, respectively). In contrast, TNF-alpha, IL-10 and IL-4 present increased amounts in BFs that were 12, 12 and 17-fold, respectively. Eighteen sera (and 10 suction BF) from normal individuals were also employed as control. Normal sera presented significantly lower serum IL-7 concentrations than BP, while no significant TGF-beta₁ variations were observed between normal and pathologic serum samples. In addition, the serum levels detected in BP patients were significantly correlated with disease intensity ( r =0.64, P =0.003, evaluated as the number of blisters/erosions for each patient) as well as with the peripheral B-lymphocyte counts ( r =0.80, P <0.001) and antibodies directed against the basement membrane zone ( r =0.65, P <0.005). Although a clear explanation of this phenomenon is lacking, the data presented in this report agree with a strong decrease of IL-7 production at the local level (keratinocyte is known to produce IL-7 and the latter is known to be down-regulated by IL-10, and in other models also by TGF-beta₁ and IL-4, whose levels are elevated in BP BFs) as opposed to an increased peripheral release of the same modulator. The IL-7 reduction may have a biological relevance in controlling a chronic, progressive disease.     

Serum levels of interleukin-18 and s-ICAM-1 in patients affected by psoriasis: preliminary considerations

OBJECTIVE: To find new aspects of the systemic involvement of the Immune System in psoriasis, we determined serum levels of interleukin-18 (IL-18) (Th1-inducing factor cytokine), CD30 (Th2 marker) and sICAM-1 (adhesion molecule). In addition we evaluated the correlation between these molecules and psoriasis area and severity index (PASI). BACKGROUND: Psoriasis is associated to an overexpression of Th1 cytokines and a relative underexpression of Th2 cytokines. IL-18 plays an important role in inducing Th1 response because it is a potent inductor of synthesis of IFN-gamma, TNF and other mediators. The two major sources of IL-18 are monocytes and macrophages but also human keratinocytes constitutively synthesized IL-18. SUBJECTS AND METHODS: We selected two groups of subjects: 16 healthy donors (HD) and 16 patients affected by psoriasis, matched for sex and age. Serum IL-18, CD30 and sICAM-1 levels were assayed by immunoenzymatic method with commercial kits. RESULTS: IL-18 and sICAM-1 levels in the patients were significantly higher than in the HDs (385.94 +/- 193.89 vs. 227.38 +/- 92.76 pg/mL, P = 0.005 and 445.00 +/- 152.67 vs. 317.88 +/- 107.20 ng/mL, P = 0.02, respectively). On the contrary, no significant difference was found between serum sCD30 levels of patients in respect to those of HDs. A significant correlation was found between serum IL-18 and PASI (Rho = 0.695, P = 0.0071), serum IL-18 and sICAM-1 (Rho = 0.543, P = 0.0356) and between sICAM-1 and PASI (Rho = 0.659, P = 0.0107).     

Oral zinc sulfate in the treatment of Behcet's disease: a double blind cross-over study

This was a randomized, controlled, double-blind trial of zinc sulfate in the treatment of Behcet's disease. Patients with Behcet's disease were recruited in this study between November 2001 and February 2003. A clinical manifestations index (CMI) was calculated for each patient. Serum zinc was estimated in all patients both at the beginning and monthly throughout the trial. Serum zinc levels were estimated from 30 healthy normal subjects matched for age and sex as a control group. Patients were randomly allocated to receive either 100 mg zinc sulfate or identical placebo tablet three times daily in a double-blind manner. After 3 months of starting treatment, patients were crossed over, that is, patients on placebo received zinc sulfate and vice versa. Mean serum zinc level in Behcet's disease patients was statistically significantly lower than mean serum zinc levels in healthy the control. In group A (started with zinc sulfate), the mean CMI started to decline directly after the first month of therapy with zinc sulfate to significantly lower levels. After shifting to placebo treatment in the fourth month, the mean of CMI started to rise again gradually but remained significantly lower than levels before therapy for the fourth and fifth months. In group B (started with placebo), the mean of CMI remained high for the first 3 months. After crossing over to zinc sulfate in the fourth month, the mean of CMI started to decrease after the fourth month. An inverse correlation between CMI and serum zinc level was found. No side-effects were seen in either group. In conclusion, zinc sulfate was found to be a good option in the treatment of Behcet's disease.     

Differential expression of interferon gamma by mitogen-stimulated peripheral blood mononuclear cells among Kuwaiti psoriasis patients

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.     

Serum levels of soluble IL-2 receptor, soluble ICAM-1, TNF-alpha, interleukin-4 and interleukin-6 in scleroderma

Background A variety of immunological markers have been reported to be elevated in patients with systemic scleroderma (SSc). Objective The aim of this study was to determine which of the following parameters: soluble IL-2 receptor (sIL-2r). soluble ICAM-1 (sICAM-1), tumour necrosis factor (TNF-alpha), interleukin-6 (IL-6) and interleukin-4 (IL-4) reflect the clinical stage of the disease and how they correlate with each other. Methods In 31 scleroderma patients the serum levels of these markers were measured in the same blood sample using ELISA test kits. The results were correlated with clinical findings such as extent of skin disease, inflammatory disease activity and involvement of internal organs. Results SIL-2r, slCAM-1 and TNF-alpha showed significant differences in subgroups of SSc patients in contrast to IL-4and IL-6, The five parameters did not correlate with each other. Conclusion sIL-2r, sICAM-1 and TNF-alpha showed differences in subgroups of scleroderma and therefore they may be useful in further studies as markers of disease activity.     

Increased serum IL-6, TNF-alpha and IL-10 levels in patients with bullous pemphigoid: relationships with disease activity

AIM: The present report analyzes the serum levels of three cytokines, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) in 15 patients with bullous pemphigoid (BP) (compared with 20 healthy controls) to evaluate a possible involvement of these biological modulators in the clinical expression of this disease. BACKGROUND: BP is a rare bullous disease of autoimmune origin with evidence of inflammatory processes that cause skin lesions with local increase of various pro-inflammatory mediators. METHODS: Determination of cytokine concentrations were obtained employing commercially available ELISA kits. RESULTS: The sera of BP patients showed increased levels of these three cytokines (P < 0.01). When the number of skin lesions (blisters and/or erosion) of each patient, employed as a marker of disease activity, was correlated with the serum levels of IL-6 and TNF-alpha, significant correlations were found (IL-6: P < 0.01 and TNF-alpha: P < 0.01, respectively), suggesting a possible role of these mediators in the development of BP blisters. The serum levels of IL-6 also correlated (P = 0.01 with those of serum C reactive protein (CRP), an acute-phase protein induced by IL-6 in hepatocytes. In addition, serum TNF-alpha and sE-selectin (an adhesion molecule previously reported to be increased by this cytokine) levels were also correlated (P < 0.05). CONCLUSIONS: On the basis of these data, it may be indicated that at least IL-6 and TNF-alpha are associated with the clinical expression of BP and that the endothelial activation (possibly induced by the TNF-alpha activity), seems to be an important phase of this dermatosis.     

Low-dose and short-term cyclosporine treatment in patients with chronic idiopathic urticaria: a clinical and immunological evaluation

The present study aimed to evaluate the effectiveness of 2.5 mg/kg/day cyclosporin (CsA) treatment in patients with severe chronic idiopathic urticaria (CIU) and the impact of CsA treatment on several cytokines involved in the etiopathogenesis of CIU. Twenty-seven CIU patients and 24 healthy control subjects were included in the study. The autologous serum skin test (ASST) for autoantibodies and urticaria activity scoring (UAS) were measured for the evaluation of the clinical severity and the response to therapy, and the serum levels of interleukin (IL)-6, IL-8, IL-2 receptor, IL-1beta, tumor necrosis factor (TNF)-alpha and IL-5 were measured. The mean UAS score was 32.07 +/- 7.05 and 6.22 +/- 3.84 before and after CsA treatment, respectively. The serum IL-2 receptor, TNF-alpha and IL-5 levels of patients before CsA treatment were statistically higher than those of the control group (P = 0.001), and after 4 weeks of CsA therapy the mean IL-2R, TNF-alpha and IL-5 levels were significantly decreased. The data from this study demonstrate that CsA therapy is efficient and safe for CIU patients. Increase in clinical efficacy and marked decreases in serum cytokine levels suggest that inhibition of cytokine generation is involved in the action of the drug in this clinical setting.     

Cytokine gene polymorphisms in psoriasis

BACKGROUND: Cytokine production is under genetic control, and certain allelic variants of cytokine genes are associated with higher or lower cytokine production in vitro and in vivo. Psoriasis is associated with an overexpression in the involved skin of T-helper cell type 1 (Th1) cytokines, e.g. interferon (IFN) -gamma and tumour necrosis factor (TNF) alpha and relative underexpression of Th2 cytokines, e.g. interleukin (IL) -4 and IL-10. Objective We investigated the hypothesis that allelic variants of genes for a high production of Th1 cytokines or TNF-alpha, or conversely low production of Th2 cytokines might represent a risk factor for developing psoriasis. METHODS: Genotyping for IFN-gamma, IL-10, IL-4 and TNF-alpha was undertaken for 84 patients with psoriasis and compared with control data on file. RESULTS: Genotype frequencies showed no differences between patients and controls for IFN-gamma, TNF-alpha or IL-4. For IL-10, patients with late onset psoriasis (over 40 years) were more likely to be heterozygous at position - 1082 (P = 0.02), corresponding to intermediate production of IL-10 in vitro and in vivo. CONCLUSIONS: Psoriasis is not determined by a genotype consistent with high production of Th1 cytokines or low production of Th2 cytokines. Thus, the Th1 cytokine profile found in psoriatic plaques is most likely a consequence of local factors.     

T细胞因子在斑秃发病中的作用

目的研究T细胞因子与斑秃发病的关系,比较活动期和稳定期斑秃患者血清T细胞因子的变化情况,并探讨斑秃患者的Th1和Th2免疫功能状况。方法107例斑秃患者,根据临床表现分为活动期和稳定期,采用夹心抗体酶联免疫吸附试验法(Sandwich,ELISA)检测活动期和稳定期组斑秃患者血清的IFN-γ、IL-2、IL-4、IL-10和IL-16水平,并分析脱发严重程度与血清细胞因子的关系,采用单因素方差分析和LSD检验。结果稳定期组血清IFN-γ水平显著高于健康对照组(P<0.05),活动期组血清IFN-γ水平与健康对照组间的差异无统计学意义(P>0.05);IL-2、IL-16水平比较,活动期组、稳定期组、健康对照组间的差异无统计学意义(P>0.05);IL-4、IL-10水平比较,稳定期组显著低于对照组,活动期组显著低于稳定期组,组间差异均有统计学意义(P<0.05);随着脱发面积占头皮面积百分比增加,患者血清IFN-γ升高(P均<0.05),IL-2、4、10、16水平的改变无明显统计学意义(P>0.05)。结论IFN-γ参与斑秃稳定期免疫反应,可能与诱导斑秃发病无关;IL-4和IL-10与病情活动有关;IL-2和IL-16可能与斑秃发病无关;IFN-γ可能与斑秃的严重程度有关。     

Study on the T-helper cell 1/2 cytokine profile in blister fluid of patients with herpes zoster and its clinical significance

Herpes zoster (HZ) is a Varicella zoster virus infection disease. Previous studies have presumed the connection between development of HZ and involvement of cellular immunity in peripheral blood. However, whether cellular immunity plays a role in the local skin lesion has not been addressed. To explore the levels of T-helper cell (Th)1/Th2 type cytokine profiles in the blister fluid of the skin lesions from the patients with HZ and its role in pathogenesis, we used the cytometric bead array kit to compare the levels of cytokines (interleukin [IL]-2, tumor necrosis factor [TNF]-α, IL-10 and IL-4) in blister fluid from 46 patients with those from the suction blister fluids from 20 volunteers without any infectious disease (the control group). The results indicated that the levels of Th1 cytokines, IL-2 and TNF-α in the blister fluid from the patients' skin lesions were significantly lower than those from the control group, whereas the levels of Th2 cytokines IL-10 and IL-4 were significantly higher than those in the control group. Moreover, significant variation of the levels of Th1/Th2 cytokines (IL-2, TNF-α, IL-10 and IL-4) in the blister fluid from the HZ patients' lesions was also observed among different stages of the disease. It is concluded that a cytokine imbalance was present in the local lesions of patients with HZ during disease development. Our data suggested that the Th immunity was associated with disease activity, which may play an important role in the pathogenesis of HZ.     

Serial measurement of serum cytokines, cytokine receptors and neopterin in leprosy patients with reversal reactions

Serum levels of cytokines (IL-4, IL-5, IFN-gamma, TNF-alpha), cytokine receptors (TNFR I and II) and one monokine (neopterin) were estimated in seven leprosy patients to establish disease associated markers for reversal reactions (RR). Sera were collected at diagnosis of leprosy, at the onset of reversal reaction and at different time points during and at the end of prednisone treatment of reactions. It was expected that the serum cytokine and monokine profile before and at different time points during reactions would provide guidelines for the diagnosis and monitoring of reversal reactions in leprosy. The cytokines and cytokine receptors were measured by ELISA, whereas a radioimmunoassay was used for neopterin measurement. Six of the seven patients showed increased levels of neopterin either at the onset of RR or 1 month thereafter, and levels declined on prednisone treatment to that seen at the time of diagnosis without reactions. No consistent disease associated cytokine profile was observed in these patients. Interestingly, serum TNF-alpha levels were increased in the same patients even after completion of prednisone treatment, indicating ongoing immune activity. In conclusion, this study demonstrates that despite cytokines levels in leprosy serum being inconsistent in relation to reversal reactions, serum neopterin measurement appears to be an useful biomarker in monitoring RR patients during corticosteroid therapy.     

寻常疣患者外周血Th17细胞相关因子的表达及意义

目的探讨Th17细胞相关因子在寻常疣患者外周血中的表达情况及意义。方法采用ELISA法检测30例寻常疣患者外周血血清中IL-17,IL-23和TGF-β1的表达水平,并以30例健康人群作为对照。结果寻常疣患者血清中IL-17及IL-23水平[分别为(206.77±48.96)pg/mL,(248.53±51.45)pg/mL]均高于正常对照组[分别为(165.49±51.84)pg/mL,(109.22±52.81)pg/mL],差异均有统计学意义(P均<0.05);寻常疣患者外周血清中TGF-β1表达水平(148.34±36.91)ng/L与正常对照组(143.64±24.36)ng/L差异无统计学意义(P>0.05)。寻常疣患者的病程、疣体数量与血清中IL-17,IL-23和TGF-β1水平均无相关性(P均>0.05)。结论 Th17细胞相关因子IL-17,IL-23及TGF-β1在寻常疣患者体内存在变化,可能与寻常疣的发病有关。     

系统性红斑狼疮患者Th1、Th2细胞因子偏移与类风湿因子和抗心磷脂抗体的相关性研究

目的评估系统性红斑狼疮(SLE)患者血清中反映Th1/Th2细胞活性的白介素12(IL-12)和白介素13(IL-13)水平的偏移,是否与循环中特异类型的类风湿因子(RF)和抗心磷脂抗体(aCL)相关.方法采用ELISA方法检测31例SLE患者和31例健康志愿者的血清IL-12、IL-13、RF和aCL,采用间接免疫荧光技术和放射免疫扩散法检测自身抗体和免疫球蛋白.结果血清IL-13水平与IgM-RF和IgM-aCL相关,相关系数分别为(0.426;P＜0.01)和(0.328;P＜0.05),但与IgA-RF,IgG-RF,IgG-aCL和总IgG,IgA和IgM水平无关联.IL-12/IL-13比率小于1组别的IgM-RF和IgM-aCL水平较其他组明显升高.结论SLE患者IgM-RF和IgM-aCL水平的升高与Th2细胞活性占优势成正相关,Th2活性优于Th1活性可能促使SLE患者自身抗体的产生.     

Cytokine gene polymorphisms in patch-stage mycosis fungoides

Cytokine production is under genetic control and certain allelic variants of cytokine genes are associated with lower or higher cytokine production in vitro and in vivo. The general concept is that a shift from a Th1 to a Th2 cytokine profile accompanies disease progression from patch-stage mycosis fungoides to tumour stage, although the results of the studies carried out have not been entirely conclusive. We aimed to investigate whether certain cytokine polymorphisms might represent a risk factor for developing patch-stage mycosis fungoides. Genotyping for IFN-gamma (Th1 cytokine), IL-6, IL-10 (Th2 cytokines), TNF-alpha and TGF-beta 1 was undertaken for 33 patients with patch-stage mycosis fungoides and the results were compared with those in a control group. Genotype distribution showed no significant differences between the patients and the controls for any of the five cytokines studied. Our study suggests that patch-stage mycosis fungoides is not determined by a specific genotype polymorphism. However, further studies on larger numbers of cases are needed before definite conclusions can be drawn.     

Both IL-4 and IL-13 inhibit the TNF-alpha and IFN-gamma enhanced MDC production in a human keratinocyte cell line,HaCaT cells

BACKGROUND: Macrophage-derived chemokine (MDC) is a Th2 type chemokine and its receptor CC chemokine receptor 4 (CCR4) is preferentially expressed on Th2 cells. Recent reports demonstrated that MDC is expressed not only by macrophages, dendritic cells and lymphocytes, but also by cultured human keratinocytes (KCs). However, the regulation of MDC production in KCs by various cytokines has not been well documented. OBJECTIVE: In this study, we investigated how Th1/Th2 cytokines regulate MDC production in a human KC cell line, HaCaT cells. METHODS: HaCaT cells were cultured with or without various cytokines for 24 h and RT-PCR was performed using these cells to evaluate MDC mRNA levels. ELISA was carried out using supernatant of HaCaT cells to calculate secreted MDC protein levels. RESULTS: MDC mRNA was weakly expressed in HaCaT cells, and upon stimulation with TNF-alpha or IFN-gamma, MDC expression was strongly upregulated. The supernatant MDC levels when stimulated with TNF-alpha or IFN-gamma were significantly higher than those without stimulation, and were synergistically increased when stimulated with a combination of TNF-alpha and IFN-gamma. Both interleukin-4 (IL-4) and IL-13 inhibited TNF-alpha and IFN-gamma enhanced MDC production in HaCaT cells in a dose-dependent manner. CONCLUSION: Th2-type cytokines IL-4 and IL-13 downregulate the production of MDC, a Th2 type chemokine, by KCs. This may partially contribute to maintaining Th1/Th2 balance in inflammatory skin diseases like atopic dermatitis.