Cytokine pattern in allergic and non-allergic chronic rhinosinusitis in asthmatic children

BACKGROUND: Rhinosinusitis represents one of the most common chronic diseases. The association of rhinosinusitis with asthma has been frequently reported. Eosinophils and Th2 cells play a pathogenic mechanism in asthma. OBJECTIVE: The aims of the study were to evaluate the cytokine pattern in chronic rhinosinusitis in asthmatic children and to compare the findings in allergic vs. non-allergic asthmatics. METHODS: Thirty-five asthmatic children were evaluated, 19 males and 16 females, with an average age of 8.7 years. All children were asthmatic and suffered from chronic rhinosinusitis. Twenty were allergic and 15 were non-allergic. Ten healthy children were studied as normal controls. Evaluated parameters were the levels of the following cytokines: IL-1beta, IL-4, IL-6, IL-8, IL-12, IFN-gamma and TNF-alpha. Cytokines were recovered from rhinosinusal lavage and measured by immunoassays. Nasal cytology was also performed in all subjects and inflammatory cells were counted by conventional staining. RESULTS: Allergic subjects showed a significant increase of IL-4 (P < 0.01) and TNF-alpha (P < 0.05) and a significant decrease of IL-12 (P < 0.05) and of IFN-gamma (P < 0.0001), whereas IL-1beta, IL-6 and IL-8 were not significantly increased. Non-allergic children showed a significant increase of IL-4 (P < 0.05) and a significant decrease of IFN-gamma (P < 0.0001), IL-12 was not significantly decreased, and IL-1beta, IL-6 and IL-8 were not significantly increased. A significant inflammatory infiltrate was present in all asthmatic children. Significant correlations were demonstrated between IL-4 and IL-12 (P < 0.001), IL-12 and IFN-gamma (P < 0.001), IL-8 and neutrophils (P < 0.01), and TNF-alpha and monocytes/macrophages (P < 0.05), in allergic asthmatics. IL-4 and IL-12 were significantly correlated (P < 0.05) as well as IL-8 and neutrophils (P < 0.01) in non-allergic asthmatics. CONCLUSION: This study shows that allergic asthmatic children with chronic rhinosinusitis have a typical Th2 cytokine pattern, but also non-allergic asthmatic children share a similar pattern. These findings would suggest the existence of a common pathophysiological mechanism shared by upper and lower airways and are consistent with the concept of united airways disease.     

Th2-type cytokines modulate IL-6 release by human bronchial epithelial cells

The multifunctional cytokine IL-6, which can be locally produced by human bronchial epithelial cells (HBECs), has been found to play a role in IL-4 dependent IgE synthesis. Since the allergic reaction in bronchial asthma is associated with the upregulation of IL-4 and Th2 type of immune response, the purpose of our study was to assess whether IL-4 and related cytokines IL-10 and IL-13 regulate IL-6 release by HBEC s. HBECs were obtained by bronchial brushing, cultured in LHC-9/RPMI 1640. At the third passage the cells were stimulated with cytokines (0.1-20 ng/ml) diluted in unsupplemented media for 24 h. The supernatants were tested for IL-6 content by sandwich ELISA. Unstimulated HBECs produced detectable amounts of IL-6 (368+/-25 pg/ml). Exposure to IL-10 (368+/-22 pg/ml) and IL-13 (395+/-6 pg/ml) resulted in little changes. IL-4 caused a slight but significant increase in IL-6 release (530+/-45 pg/ml), P<0.05, TNFalpha (1657+/-85 pg/ml) and IFNgamma (1953+/-37 pg/ml) showed strong induction of IL-6 release in HBECs (P<0.005 and P<0.001, respectively). Both IL-4 and IL-13 significantly inhibited TNF induced IL-6 release (P<0.01 for both) while augmenting the effect of IFNgamma (P<0.005 and P<0.01, respectively.). IL-10 was without a significant effect. We conclude that Th2-type cytokines IL-4 and IL-13 affect the release of IL-6 by HBECs in response to TNFalpha (inhibition) and IFgamma (augmentation). IL-10 had no effect on the regulation of IL-6 release. Modulation of IL-6 levels by Th2-type cytokines may play a role in allergic reactions through the IL-6 promoting effect on IL-4 mediated IgE production.     

Soluble interleukin-2 receptor and interleukin-4 in sera of asthmatic children before and after a prednisolone course.

BACKGROUND: Cytokine-mediated interactions among inflammatory cells may play a role in the pathogenesis of bronchial asthma. OBJECTIVE: To understand the role of soluble interleukin-2 receptor (sIL-2R) and interleukin-4 (IL-4) in the disease activity of acute asthma, changes in serum concentrations of sIL-2R and IL-4 elaborated by activated T-lymphocyte before and after prednisolone therapy with clinical improvement were determined in the present study. METHODS: Circulating levels of sIL-2R and IL-4 in sera from 15 normal control subjects and in sera from 20 allergic asthmatic children with acute exacerbation and in a stable condition were determined by using commercially available ELISA kits. RESULTS: The mean concentration of serum sIL-2R was significantly higher in acute exacerbation than in children with stable asthma (368.9 +/- 395.4 pg/mL vs 291.2 +/- 361.0 pg/mL; P < .01) or in control subjects (124.6 +/- 17.8 pg/mL; P < .001). The mean concentration of serum IL-4 was higher in acute exacerbation (5.82 +/- 1.10 pg/mL) and in stable asthmatic patients (6.73 +/- 2.83 pg/mL) versus control group subjects (5.54 +/- 1.20 pg/mL). However, the difference was not statistically significant among the three study groups. CONCLUSIONS: This study provides further evidence that changes in serum IL-2R may serve as an objective indicator for clinical outcome of allergic asthmatic patients.     

Interleukin (IL)-2 and IL-12 responses to Chlamydia trachomatis infection in adolescents

Chlamydia trachomatis infects epithelial cells at the mucosal surface. While in vitro and animal studies have shown changes in mucosal T(H)1-associated cytokines in the presence of C. trachomatis infection and with its progression to the upper genital tract or clearance, in vivo cytokine responses to chlamydial infection in humans are not well understood. Using a quantitative enzyme-linked immunosorbent assay (ELISA), we examined the endocervical production of two T(H)1-associated cytokines, i.e. interleukin (IL)-2 and IL-12, in relation to C. trachomatis infection in adolescents. At a randomly selected visit for 396 females, median endocervical IL-2 levels were significantly lower (190 versus 283 pg/ml, P = 0.02) and median IL-12 levels significantly higher (307 versus 132 pg/ml, P < 0.001) in subjects testing positive versus negative for C. trachomatis. These divergent T(H)1-associated cytokine responses were: (1) confirmed in paired analyses of 96 individuals before and after infection within 6-month intervals, (2) reversible in 97 patients who cleared infection during consecutive visits, (3) not attributable to sociodemographic factors or other genital infections and (4) independent of common genetic variants at the IL2 and IL12B loci associated previously with differential gene expression. From these findings we infer that increased IL-12 and decreased IL-2, observed commonly during mucosal inflammation, are important features of mucosal immune defence against C. trachomatis infection.     

Role of Th1 and Th2 cytokines in immune response to uncomplicated Plasmodium falciparum malaria

The relative balance between Th1 and Th2 cytokines appears crucial, since the role of cytokines has been evaluated in several studies by comparison of clinically heterogeneous groups of patients. The aim of this study is to determine the role of proinflammatory Th1 cytokines, interleukin-12 (IL-12) and gamma interferon (IFN-gamma), and anti-inflammatory Th2 cytokines, IL-4 and IL-10, in a homogeneous group of patients with uncomplicated Plasmodium falciparum malaria. Levels of IL-12, IFN-gamma, Il-4, and IL-10 in serum for 20 adult patients and 15 healthy control subjects were determined by an immunoenzymatic assay. Serum levels of Th1 cytokines, IL-12 (8.6 +/- 2.8 pg/ml; controls, 3.2 +/- 0.7 pg/ml) and IFN-gamma (39.2 +/- 67.6 pg/ml; controls, 8.4 +/- 6.3 pg/ml), were significantly increased at admission; 3 days later, levels of IL-12 in serum remained significantly high (8.8 +/- 2.6 pg/ml), whereas IFN-gamma levels returned to control values. The anti-inflammatory response of Th2 cytokines (IL-10 and IL-4) was distinct. Levels of IL-10 in serum were not significantly increased at day 0 and day 3 (306.6 +/- 200.4 pg/ml and 56.6 +/- 38.4 pg/ml, respectively; controls, 17.4 +/- 9.0 pg/ml). In contrast, levels of IL-4 in serum were not increased on admission (3.4 +/- 1.2 pg/ml; controls, 2.4 +/- 0.8 pg/ml), but at day 3 a moderate and significant increase of IL-4 levels was observed (4.5 +/- 1.7 pg/ml). In conclusion, the increase of Th1 cytokine IL-12 and IFN-gamma levels during the acute phase of uncomplicated P. falciparum malaria may reflect an early and effective immune response regulated by proinflammatory Th1 cytokines, and in particular IFN-gamma may play a role in limiting progression from uncomplicated malaria to severe and life-threatening complications.     

Interleukin (IL)-4, IL-13, and IL-17A differentially affect the profibrotic and proinflammatory functions of fibrocytes from asthmatic patients

Fibrocytes contribute to the fibrotic changes most frequently observed in forms of asthma where inflammation is driven by T helper type 2 (Th2) cells. The mechanisms that regulate the profibrotic function of asthmatic fibrocytes are largely unknown. We isolated circulating fibrocytes from patients with allergen-exacerbated asthma, who showed the presence of fibrocytes, together with elevated concentrations of interleukin (IL)-4 and IL-13 and slightly increased concentrations of the Th17 cell-derived IL-17A, in induced sputum. Fibrocytes stimulated with IL-4 and IL-13 produced high levels of collagenous and non-collagenous matrix components and low levels of proinflammatory cytokines. Conversely, fibrocytes stimulated with IL-17A proliferated and released proinflammatory factors that may promote neutrophil recruitment and airway hyperresponsiveness. IL-17A also indirectly increased α-smooth muscle actin but not collagen expression in fibrocytes. Thus, fibrocytes may proliferate and express a predominant profibrotic or proinflammatory phenotype in asthmatic airways depending on the local concentrations of Th2- and Th17-derived cytokines.     

Circulating antiinflammatory cytokine IL-10 in patients with inflammatory bowel disease (IBD).

IBD is characterized by increased serum concentrations of different cytokines. IL-10 inhibits the production of proinflammatory cytokines such as IL-1, tumour necrosis factor-alpha (TNF-a), interferon-gamma (IFN-gamma) and IL-6 through inhibitory action on Th1 cells and macrophages, and it is thought to be a suppressor type cytokine. In the present study we determined serum concentrations of IL-10 in patients with ulcerative colitis (UC) and Crohn's disease (CD). We measured human IL-10 by our own newly established ELISA system using PharMingen antibodies. Serum antibodies were assessed in 44 patients with UC, 40 patients with CD, and in 30 healthy controls. Human IL-10 serum levels were significantly increased in patients with active UC (144 +/- 34 pg/ml (mean +/- s.e.m.), P < 0.001) and in active CD (132 +/- 32 pg/ml, P < 0.001) compared with healthy controls (44 +/- 9.5 pg/ml). Only patients with active CD and active UC presented with significantly increased IL-10 serum levels, while patients with inactive disease did not show any significant increase. There was no statistically significant difference between IL-10 serum levels in patients with CD or UC. Compared with clinical disease activity indices there was a significant correlation between IL-10 serum concentration and CDAI in patients with CD (r = 0.45, P < 0.01) and CAI in UC patients (r = 0.39, P < 0.05). Comparing IL-10 serum levels with serum concentrations of other proinflammatory cytokines there was a significant correlation to serum levels of sIL-2R (r = 0.417, P < 0.05) and IL-6 (r = 0.387, P < 0.05) in patients with CD. Serum cytokine levels in patients with UC did not show any significant correlation to IL-10 serum concentration. IL-10 is elevated in serum of patients with active CD and UC, suggesting that IL-10 acts as a naturally occurring damper in the acute inflammatory process of IBD.     

IL-10 serum levels in children with moderate asthma

Levels of an interleukin 10 (IL-10) are reduced in asthmatic patients in comparison to healthy subjects. Fact, that IL-10 is produced by Th1 and that inhibits cytokine production by Th2 lymphocytes has led to the concept that IL-10 might be beneficial in mitigating allergic inflammation. The purpose of this study was to define the effect of 4 week monotherapy with triamcinolone acetonide or nedocromil sodium on the serum level of IL-10, bronchial hyperresponsiveness and clinical parameters in atopic asthma children. It was an 8 week, randomised, double-blind trial of 37 children with moderate asthma allergic to house dust mite. Patients were randomly allocated to receive 200 mcg triamcinolone twice daily (n = 18), or 0.004 g nedocromil four times daily (n = 19). Thirty children completed the study. After treatment with triamcinolone the level of IL-10 in blood serum significantly increased, bronchial hyperreactivity significantly decreased, and all clinical parameters improved. Mean IL-10 levels in serum before and after treatment with triamcinolone were 7.5 pg/ml with 95%CI 6.79%-8.22% and 14.21 pg/ml with 95%CI 11.33%-17.09% respectively (p < 0.001). After treatment with nedocromil, clinical symptoms improved significantly, IL-10 serum levels and bronchial hyperreactivity did not change significantly (p = 0.094 and p = 0.09 respectively). This study demonstrates that one possible way by which triamcinolone contribute to inhibition of inflammation is by effect on IL-10.     

Gram-positive bacteria are potent inducers of monocytic interleukin-12 (IL-12) while gram-negative bacteria preferentially stimulate IL-10 production

Interleukin-10 (IL-10) and IL-12 are two cytokines secreted by monocytes/macrophages in response to bacterial products which have largely opposite effects on the immune system. IL-12 activates cytotoxicity and gamma interferon (IFN-gamma) secretion by T cells and NK cells, whereas IL-10 inhibits these functions. In the present study, the capacities of gram-positive and gram-negative bacteria to induce IL-10 and IL-12 were compared. Monocytes from blood donors were stimulated with UV-killed bacteria from each of seven gram-positive and seven gram-negative bacterial species representing both aerobic and anaerobic commensals and pathogens. Gram-positive bacteria induced much more IL-12 than did gram-negative bacteria (median, 3,500 versus 120 pg/ml at an optimal dose of 25 bacteria/cell; P < 0.001), whereas gram-negative bacteria preferentially stimulated secretion of IL-10 (650 versus 200 pg/ml; P < 0.001). Gram-positive species also induced stronger major histocompatibility complex class II-restricted IFN-gamma production in unfractionated blood mononuclear cells than did gram-negative species (12,000 versus 3,600 pg/ml; P < 0.001). The poor IL-12-inducing capacity of gram-negative bacteria was not remediated by addition of blocking anti-IL-10 antibodies to the cultures. No isolated bacterial component could be identified that mimicked the potent induction of IL-12 by whole gram-positive bacteria, whereas purified LPS induced IL-10. The results suggest that gram-positive bacteria induce a cytokine pattern that promotes Th1 effector functions.     

Differences in cytokine production by peripheral blood mononuclear cells (PBMC) between patients with atopic dermatitis and bronchial asthma.

It is widely accepted that type 2 helper T (Th2) lymphocytes play a crucial role in the pathogenesis of atopic dermatitis (AD) as well as bronchial asthma (BA). We measured the amounts of IL-5 and interferon-gamma (IFN-gamma) produced by PBMC upon stimulation with house dust mite (HDM) or Candida albicans (CA) in 17 children (3-15 years) with AD, and compared these values with those of 16 children with BA. Although IL-5 production by PBMC upon stimulation with HDM in patients with AD was significantly higher than that in 13 non-atopic controls (geometric mean = 23.4 pg/ml versus 5.9 pg/ml, P < 0.05), it was significantly lower than that in patients with BA (177.8 pg/ml, P < 0.001). The amount of IL-5 produced by PBMC upon stimulation with CA was also significantly lower in patients with AD than in those with BA (7.2 pg/ml versus 100.0 pg/ml, P < 0.001). The production of IFN-gamma by PBMC stimulated with HDM or CA was also significantly lower in patients with AD than in those with BA (HDM 4. 3 pg/ml versus 12.6 pg/ml, P < 0.05; CA 6.5 pg/ml versus 60.3 pg/ml, P < 0.001). Consequently the ratio of IL-5 to IFN-gamma production was high not only in patients with BA but also in those with AD. These findings suggest that there are some differences in the regulation of in vivo cytokine production between patients with AD and those with BA, although a Th2-dominant profile is common to both.     

IL-17 is increased in asthmatic airways and induces human bronchial fibroblasts to produce cytokines.

BACKGROUND: IL-17 is a cytokine that has been reported to be produced by T lymphocytes. In vitro, IL-17 activates fibro-blasts and macrophages for the secretion of GM-CSF, TNF-alpha, IL-1beta, and IL-6. A number of these cytokines are involved in the airway remodeling that is observed within the lungs of asthmatic individuals. OBJECTIVE: In this study, we investigated the expression of IL-17 in sputum and bronchoalveolar lavage specimens obtained from asthmatic subjects and from nonasthmatic control subjects. METHODS: IL-17 was detected through use of immunocytochemistry, in situ hybridization, and Western blot. Bronchial fibroblasts were stimulated with IL-17, and cytokine production and chemokine production were detected through use of ELISA and RT-PCR. RESULTS: Using immunocytochemistry, we demonstrated that the numbers of cells positive for IL-17 are significantly increased in sputum and bronchoalveolar lavage fluids of subjects with asthma in comparison with control subjects (P <.001 and P <.005, respectively). We demonstrated that in addition to T cells, eosinophils in sputum and bronchoalveolar lavage fluids expressed IL-17. Peripheral blood eosinophils were also positive for IL-17, and the level of IL-17 in eosinophils purified from peripheral blood was significantly higher in subjects with asthma than in controls (P <.01). To further investigate the mechanism of action of IL-17 in vivo, we examined the effect of this cytokine on fibroblasts isolated from bronchial biopsies of asthmatic and nonasthmatic subjects. IL-17 did enhance the production of pro-fibrotic cytokines (IL-6 and IL-11) by fibroblasts, and this was inhibited by dexamethasone. Similarly, IL-17 increased the level of other fibroblast-derived inflammatory mediators, such as the alpha-chemokines, IL-8, and growth-related oncogene-alpha. CONCLUSION: Our results, which demonstrate for the first time that eosinophils are a potential source of IL-17 within asthmatic airways, suggest that IL-17 might have the potential to amplify inflammatory responses through the release of proinflammatory mediators such as alpha-chemokines.     

特异性免疫治疗对哮喘和鼻炎患者血清炎性细胞因子的影响

目的通过检测对屋尘螨过敏的的哮喘和/或鼻炎患者在特异性免疫治疗或常规药物治疗过程中血清白介素(IL)-5、IL-10、IL-17、INF-γ及TNF-α等5种细胞因子的水平,探讨特异性免疫治疗对过敏性哮喘和鼻炎患者血清炎性细胞因子的影响。方法选取44例在广州呼吸疾病研究所接受标准化屋尘螨特异性免疫治疗(SIT)满1年的哮喘和/或鼻炎患者作为SIT组,50例对屋尘螨过敏并未接受SIT治疗的哮喘和/或鼻炎患者作为病例组,另外选取23例无过敏、无哮喘与鼻炎的健康自愿者作为对照组,用悬浮芯片方法检测三组人群血清中IL-5、IL-10、IL-17、INF-γ及TNF-α等5种细胞因子的水平。结果服从正态分布的数据以均数±标准差表示,偏态分布的数据以中位数(四分位间距数)表示。FEV1%(%)在SIT组、病例组及对照组中分别为93.05±15.62、87.0±13.51、95.51±7.84,三组比较显示无显著差异(P>0.05);AHR在这三组中分别为2(0,3)、1(0,2)、0(0,0),三组比较显示SIT组及病例组均显著高于对照组(P<0.05),SIT组与病例组比较无显著差异(P>0.05);血清IL-5(pg/mL)在SIT组、病例组及对照组中的水平分别为1.46(0.62,2.71)、1.95(1.18,2.46)、0.34(0.01,0.83),其中SIT组显著低于病例组(P=0.001),病例组显著低于对照组(P<0.001);IL-10(pg/ml)在SIT组、病例组及对照组中的水平分别为1.6(0.95,2.69)、1.25(0.93,1.8)、0.43(0.21,1.07),SIT组与病例组显著高于对照组(P<0.001);TNF-α(pg/mL)在SIT组、病例组及对照组中的水平分别为10.81(2.18,31.3)、3.39(1.78,6.83)、0.09(0.09,1.18),其中SIT组显著高于病例组与对照组(P=0.004),病例组又显著高于对照组(P<0.001)。IL-17与INF-γ在三组受试者的血清中均不可测出。结论哮喘和鼻炎患者血清中IL-5、TNF-α水平显著高于正常人,说明IL-5和TNF-α在哮喘和/或鼻炎的致病中发挥重要作用;关于SIT对炎性细胞因子的影响还有待我们进一步的研究。     

Parental tobacco smoking is associated with augmented IL-13 secretion in children with allergic asthma

BACKGROUND: Exposure to environmental tobacco smoke (ETS) has been shown to increase symptoms of allergic bronchial asthma, but direct effects on the expression of inflammatory markers have not been demonstrated thus far. OBJECTIVE: The aim of this study was to assess the correlation of ETS exposure with the expression of proinflammatory mediators in airway secretions, including IFN-gamma and IL-12, as well as IL-5 and IL-13, in allergic asthmatic schoolchildren and healthy control subjects. METHODS: By using the nasopharyngeal aspiration technique, airway secretions were collected from 24 atopic children with asthma (age, 6-16 years) and 26 healthy control subjects, and the concentration of cytokines was measured with immunoenzymatic methods. RESULTS: IL-13 levels were highly increased in patients with asthma (P < .005), and parental tobacco smoke resulted in a significant increase in airway IL-13 secretion in these children compared with that seen in nonexposed children and healthy control subjects (median, 860 pg/mL vs 242 pg/mL and 125 pg/mL, respectively). Furthermore, a positive correlation between IL-13 levels and serum IgE concentrations (r(s) = 0.55) was found in children with allergic asthma. CONCLUSIONS: These results indicate that ETS augments the expression and secretion of IL-13 in allergic asthma and that nasopharyngeal aspiration is a suitable method to assess cytokine measurements in airways in children. Measurements of IL-13 in secretions might be taken into account as a noninvasive marker of airway inflammation and to assess the detrimental effects of ETS.     

Serum IL-23 Strongly and Inversely Correlates with FEV(1) in Asthmatic Children

Background: Recently, Th17 cells have been found to participate in the pathogenesis of allergic asthma. IL-23 is a cytokine that may be implicated in modulating Th17 response. This study aimed at evaluating IL-23 and relating it to lung function in asthmatic children. Methods: Seventy-eight asthmatic children and 40 healthy children were evaluated. Spirometry and serum IL-23 measurement (ELISA kit) were performed in all asthmatic children. Results: IL-23 levels were higher in asthmatic than in healthy children (p < 0.001). There was a strong inverse relationship between FEV(1) and IL-23 (r = -0.787). Conclusions: This preliminary study suggests that serum IL-23 could be a suitable marker of bronchial function impairment in allergic asthmatic children.     

Proinflammatory cytokine (IL-1beta, IL-6, IL-12, IL-18 and TNF-alpha) levels in sera of patients with subacute cutaneous lupus erythematosus (SCLE)

Subacute cutaneous lupus erythematosus (SCLE) is a subset of lupus erythematosus that identifies patients with clinically recognized erythematous, nonscarring lesions, photosensitivity and serologic abnormalities. Anti-Ro (SS-A) antibodies are considered to be a typical immunopathologic marker of SCLE. Autoimmune diseases have been also characterized by the disturbances in the cytokine network. The aim of this study was to compare the concentrations of proinflammatory cytokines (IL-1beta, IL-6, IL-12, IL-18 and TNF-alpha) in serum of ANA-positive (antibody against nuclear antigen) and ANA-negative patients with SCLE. Sera samples were collected from 15 patients with SCLE (9 ANA-positive and 6 ANA-negative ones). The preliminary identification of autoantibodies as well as their titers was determined on HEp-2 cells using IIF method. Western blotting (EUROIMMUN) was applied to verify the results of IIF. Proinflammatory cytokine concentrations in the patients' sera samples were determined by enzyme-linked immunosorbent assay (ELISA) (Bender MedSystems). The levels of IL-12 were higher in ANA-positive patients than in ANA-negative subgroups [median (interquartile range), 330 pg/ml (128-708 pg/ml) versus 39.4 pg/ml (31.25-80 pg/ml)]. Similar differences were observed in the level of IL-18 [median (interquartile range), 508.4 pg/ml (180-1222 pg/ml) versus 100.5 pg/ml (78.1-154 pg/ml)]. The differences in TNF-alpha levels between the groups of ANA-positive and ANA-negative patients were at the verge of statistical significance, p<0.05. The sera levels of IL-1beta and IL-6 were low and of no significant difference concerning the ANA-positive and ANA-negative subgroups. Since serum levels of IL-12 and IL-18 were higher in ANA-positive patients than in ANA-negative patients, these cytokines might play an important role in the inflammatory process in SCLE.     

Expression of interleukin (IL)-4 and IL-5 proteins in asthma induced by toluene diisocyanate (TDI)

Background TDI-induced asthma exhibits clinical, functional and morphological similarities with allergen-induced asthma, suggesting that an immunological mechanism is involved in the sensitization to TDL In vitro studies using the technique of cloning lymphocytes demonstrated that a great proportion of T-cell clones derived from bronchial mucosa of subjects with TDI-induced asthma produced IL-5 and interferon-gamma, but not IL-4, upon in vitro stimulation. Objectives To investigate in vivo the role of IL-4 and IL-5 on the inflammatory response of the bronchial mucosa to TDI in sensitized subjects, we performed a quantitative analysis of bronchial biopsies. Methods We obtained bronchial biopsies from six subjects with TDI asthrha 48 h after an asthmatic reaction induced by TDI challenge (challenged group), in six subjects with TDI asthma 1–4 weeks after the last exposure to TDI (chronic group), and in six non-asthmatic controls. The number of eosinophils, mast cells, T-lymphocytes, and IL-4 and IL-5 protein positive cells was determined by immunohistochemistry in the area 100 μn beneath the epithelial basement membrane. Results The characteristic increase of submucosal eosinophils, but not of mast cells and T-lymphocytes, was observed in the subjects with TDI-induced asthma when compared with controls. No differences were detected between the two groups of asthmatics. In the subjects with TDI-induced asthma, cell immunoreactivity for IL-5 was increased when compared with normal controls. There was no difference in the expression of IL-5 protein between challenged and chronic asthmatics. In contrast, the expression of IL-4 protein was increased only in the asthmatic subjects tested after recent exposure to TDI. Conclusions We demonstrated that TDI asthma 48 h after specific bronchial challenge was associated with increased numbers of cells expressing IL-4 and IL-5, whereas chronic TDI asthma was associated with increased expression of IL-5, but not of IL-4. The results suggest that subjects who developed TDI asthma exhibit increased production of IL-5 even in the absence of a recent trigger by the exogenous sensitizer and that production of TH₂-like cytokines in TDI-induced asthma may not always be co-ordinately regulated in vivo.     

恶性淋巴瘤患者TH 1/TH 2细胞因子表达水平的研究

目的 探讨恶性淋巴瘤患者血清中TH1/TH2细胞因子变化及其临床意义,为肿瘤的免疫治疗提供实验依据.方法 用流式细胞小球微阵列术(cytometric bead array,CBA)检测92例恶性淋巴瘤患者及70例健康人群血清中γ干扰素(IFN-γ)、肿瘤坏死因子-α仪(TNF-α)、白细胞介素(IL-2、IL-4、IL-5、IL-10)表达水平.结果 92例恶性淋巴瘤患者血清中TH1型细胞因子的水平分别为:IFN-γ(34.26±33.4g)pg/ml、TNF-α(8.17±10.09)pg/ml、IL-2(3.74 4±1.72)pg/ml;TH2型细胞因子的水平分别为:IL-10(6.28±8.56)pg/ml、IL-5(3.53±3.20)pg/ml、IL-4(6.22±7.13)pg/ml.除TNF-α表达水平降低外,其余5项均明显高于健康体检组,差异有统计学意义(P＜0.01).TH1细胞因子IL-2与TH2细胞因子IL-4的比值明显下降(0.78±O.44),与健康体检组(1.09±0.45)比较差异有统计学意义(P＜0.01).IL-10与疾病的进展相关,Ⅲ/Ⅳ期恶性淋巴瘤患者的表达水平为(9.58±13.96)pg/ml,Ⅰ/Ⅱ期的表达水平为(4.77±3.50)pg/ml,二者比较差异有统计学意义(P＜0.01).IFN-γ在大于60岁的恶性淋巴瘤患者中表达水平明显降低,与其他年龄段恶性淋巴瘤患者比较差异有统计学意义(P ＜0.05).结论 恶性淋巴瘤患者血清中TH1/TH2细胞因子平衡失调,检测TH1/TH2细胞因子可作为评价淋巴瘤临床进展及预后指标.TH1/TH2平衡向TH2方向漂移,这可能是肿瘤细胞发生免疫逃逸,从而导致肿瘤的发生或者转移的原因之一.     

Increased prostaglandin E2 levels in the airway of patients with eosinophilic bronchitis

Background: Eosinophilic bronchitis is a common cause of chronic cough, which like asthma is characterized by sputum eosinophilia, but unlike asthma there is no variable airflow obstruction or airway hyperresponsiveness. We tested the hypothesis that the different airway function in patients with eosinophilic bronchitis and asthma could be caused by an imbalance in the production of bronchoconstrictor (LTC₄) and bronchoprotective (prostaglandin E₂; PGE₂) lipid mediators. Methods: We measured cytokines levels, proinflammatory mediators and eicosanoids concentration in sputum from 13 subjects with nonasthmatic eosinophilic bronchitis, 13 subjects with asthma, and 11 healthy control subjects. Cytokines mRNA levels were measured by real time PCR, proinflammatory mediators, PGE₂, and LTC₄ were measured by enzyme immunoassays. Results: The median sputum eosinophil count was not statistically different in patients with asthma (7.95%) and eosinophilic bronchitis (15.29%). The levels of mRNA specific to interleukin‐5 (IL‐5), IL‐4, IL‐10, IL‐13, interferon γ (IFN‐γ), IL‐2, vascular endothelial growth factor and transforming growth factor β were similar in both conditions. In addition, no differences were found between asthma and eosinophilic bronchitis in proinflammatory cytokines, such as IL‐8, IFN‐γ and tumor necrosis factor α (TNF‐α) levels. Sputum cysteinyl‐leukotrienes concentration was raised both in eosinophilic bronchitis and asthma patients. We found that induced sputum PGE₂ concentrations were significantly increased in subjects with eosinophilic bronchitis (838.3 ± 612 pg/ml) when compared with asthmatic (7.54 ± 2.14 pg/ml) and healthy subjects (4 ± 1.3 pg/ml). Conclusion: This data suggest that the difference in airway function observed in subjects with eosinophilic bronchitis and asthma could be due to differences in PGE₂ production in the airways.