Elevation of serum soluble intercellular adhesion molecule-1 (sICAM-1) and sE-selectin levels in bronchial asthma.

Adhesion molecules such as ICAM-1 and E-selectin have been shown to play important roles in the production of allergic inflammation. In the present study, we measured serum soluble ICAM-1 (sICAM-1) and soluble E-selectin (sE-selectin) levels by ELISA in 42 patients with bronchial asthma (22 atopic and 20 non-atopic) during asthma attacks and in stable conditions in order to assess the state of ICAM-1 and E-selectin in allergic inflammation. Both serum sICAM-1 levels and serum sE-selectin levels in sera obtained during bronchial asthma attacks were higher than those in sera obtained in stable conditions. These findings were observed regardless of atopic status. To examine the regulatory mechanism in the elevation of serum sICAM-1 and sE-selectin levels, serum tumour necrosis factor-alpha (TNF-alpha) levels were measured by ELISA. TNF-alpha levels in sera obtained during bronchial asthma attacks were higher than those in sera obtained in stable conditions. There was a correlation between the nature of change in serum TNF-alpha levels and the nature of change in serum sICAM-1 levels or serum sE-selectin levels, though serum TNF-alpha levels did not correlate with serum sICAM-1 levels or serum sE-selectin levels. These results suggest that higher levels of sICAM-1 and sE-selectin during asthma attacks may reflect the up-regulation of ICAM-1 and E-selectin expression in allergic inflammation, and that the soluble form of these adhesion molecules may be useful markers for the presence of allergic inflammation. TNF-alpha is shown to enhance the expression and release of ICAM-1 and E-selectin in vitro, however; the regulatory mechanism in the elevation of serum sICAM-1 and sE-selectin levels remains to be clarified.     

Elevation of serum soluble vascular cell adhesion molecule-1 (sVCAM-1) levels in bronchial asthma.

We have previously shown the elevation of serum soluble intercellular adhesion molecule-1 (sICAM-1) and soluble E-selectin (sE-selectin) in patients with bronchial asthma during asthma attacks. In the present study, we extended our earlier study by measuring serum sVCAM-1 levels by ELISA in 45 patients with bronchial asthma (23 atopic and 22 non-atopic) during asthma attacks and in stable conditions in order to assess further the state of adhesion molecules in allergic inflammation of bronchial asthma. The levels of sVCAM-1 in sera obtained during bronchial asthma attacks were higher than those in sera obtained in stable conditions. These findings were observed regardless of atopic status. To examine the regulatory mechanism in the elevation of serum sVCAM-1 levels, serum tumor necrosis factor-alpha (TNF-alpha) levels were measured by ELISA. TNF-alpha levels in sera obtained during bronchial asthma attacks were higher than those in sera obtained in stable conditions. The nature of change in serum TNF-alpha levels correlated with the nature of change in serum sVCAM-1 levels, but serum TNF-alpha levels did not correlate with serum sVCAM-1 levels. These results suggest that higher levels of sVCAM-1 during asthma attacks may reflect the up-regulation of VCAM-1 expression in allergic inflammation, and that a soluble form of VCAM-1 molecules may be useful markers for the presence of allergic inflammation. TNF-alpha is shown to enhance the expression and release of VCAM-1 in vitro, however; the regulatory mechanism in the elevation of serum sVCAM-1 levels remains to be clarified.     

Soluble intercellular adhesion molecule-1 in sera of children with bronchial asthma exacerbation.

Previous studies have suggested that intercellular adhesion molecule-1 (ICAM-1; CD54) may be involved in the pathogenesis of asthma. In addition, a soluble form of intercellular adhesion molecule-1 (sICAM-1) has been detected in increased concentrations in the sera from adult patients with certain inflammatory, immune, or malignant diseases. To determine whether bronchial asthma exacerbation in children is associated with increased levels of serum sICAM-1 and to investigate the effect of the severity of exacerbation on these levels, the concentrations of sICAM-1 were measured in sera of 20 healthy control children and 45 asthmatic children (15 with mild, 15 with moderate, and 15 with severe asthma exacerbation) using an immunoenzymatic assay. Assessment of the severity of asthma exacerbation was based on clinical and physiological parameters. The mean (+/- SD) level of serum sICAM-1 for asthmatic children (390.0+/-108.3 ng/ml) was significantly higher than that for healthy (193.2+/-33.95 ng/ml; p = 0.000). We have also found a differential rise of serum sICAM-1 level which correlates well with the severity of asthma exacerbation. The elevated concentrations of serum sICAM-1 in acute bronchial asthma may reflect the extensive inflammatory response occurring in the airways during acute exacerbation of the disease with airway obstruction. The results of this study suggest that serum sICAM-1 is a promising serological marker of the severity of inflammation in bronchial asthma in children and it would not only facilitate staging of inflammation but also allow the monitoring of therapy and intervention.     

Elevation of serum soluble tumour necrosis factor (TNF) receptor and IL-1 receptor antagonist levels in bronchial asthma

The specific inhibitor for TNF-α activity, soluble form of the 55-kD TNF receptor (sTNF-RI) and soluble form of the 75-kD receptor (sTNF-RII), and the specific inhibitor for IL-1 activity, IL-1 receptor antagonist (IL-1Ra), have been identified. It has been shown that the levels of these inhibitors are elevated in plasma/serum and biological fluids in several diseases, and the protective and inhibitory effect of these inhibitors exist in several inflammatory diseases. In the present study, we measured serum levels of sTNF-RI, STNF-RII and IL-1Ra by ELISA in 36 patients with bronchial asthma (16 atopic and 20 non-atopic) during asthma attacks and in stable conditions in order to assess the state of these inhibitors in allergic inflammation. The levels of sTNF-RI, sTNF-RII and IL-1Ra in sera obtained during bronchial asthma attacks were higher than those in sera obtained in stable conditions. These findings were obtained regardless of atopic status. These results suggest that higher levels of serum sTNF-RI, sTNF-RII and IL-1Ra may reflect up-regulation of TNF-R expression and IL-1Ra production in allergic inflammation, and sTNF-RI, sTNF-RII and IL-1Ra may contribute to regulating TNF-α- and IL-1-mediated production and development of allergic inflammation.     

Intercellular adhesion molecule 1 and tumor necrosis factor alpha in asthma and persistent allergic rhinitis: relationship with disease severity.

BACKGROUND: Tumor necrosis factor alpha (TNF-alpha) is involved in the up-regulation of intercellular adhesion molecule 1 (ICAM-1). Allergic rhinitis is often associated with bronchial hyperresponsiveness. OBJECTIVE: We investigated the relationship between allergic airway disease severity and serum concentrations of soluble ICAM-1 (sICAM-1) and TNF-alpha and nasal expression of ICAM-1. METHODS: Serum concentrations of TNF-alpha and sICAM-1 were investigated in 85 adults with persistent rhinitis and 90 patients with asthma. Seventy patients with rhinitis were challenged with methacholine. Nasal biopsy for ICAM-1 expression was performed in 6 patients with moderate-severe rhinitis and in 6 patients with mild rhinitis. RESULTS: In patients with rhinitis, serum sICAM-1 concentrations were as follows: group without bronchial hyperresponsiveness (n = 29), 206.85 ng/mL; group with bronchial hyperresponsiveness but without asthma symptoms (n = 20), 233.39 ng/mL; and group with newly recognized asthma (n = 21), 260.06 ng/mL. The sICAM-1 level was significantly lower in patients with mild rhinitis (216.21 ng/mL) than in patients with moderate-severe rhinitis (244.08 ng/mL). Nasal ICAM-1 expression was significantly higher in the moderate-severe rhinitis group than in the mild rhinitis group. In patients with asthma, serum concentrations of sICAM-1 were as follows: patients with mild asthma, 272.8 ng/mL; patients with moderate asthma, 340.16 ng/mL; patients with severe asthma without oral corticosteroids therapy, 426.74 ng/mL; and patients with severe asthma with oral corticosteroids therapy, 314 ng/mL. The serum TNF-alphaa concentration differed between patients with rhinitis (n = 15) (1.065 pg/mL) and patients with asthma (n = 12) (3.46 pg/mL). Among patients with asthma, TNF-alpha concentrations were similar in all groups classified according to the disease severity. CONCLUSIONS: sICAM and ICAM-1 expression correlates with airways diseases severity.     

Soluble Intercellular Adhesion Molecule-1 (ICAM-1) Antigen in Patients with Rheumatoid Arthritis

Intercellular adhesion molecule-1 (ICAM-1), a member of the immunoglobulin supergene family, is known to play an important role in inflammatory diseases. Using a previously developed enzyme-linked immunosorbent assay (ELISA) with two monoclonal antibodies (MoAbs) against human ICAM-1, levels of soluble ICAM-1 (sICAM-1) were measured in sera from patients with collagen diseases and in synovial fluids (SF) from patients with rheumatoid arthritis (RA). Although the results did not demonstrate that RA and other collagen diseases, as a group, had significantly higher levels of sICAM-1 in sera as compared with healthy controls, 21 of 138 cases (15%) with collagen diseases and 11 out of 57 patients (19%) with RA clearly showed higher levels of sICAM-1 in the sera. Comparisons between RA patients of radiological stages I and II and between stage I and other stages showed significantly higher levels of sICAM-1 in the sera of patients in the latter stages. RA patients with vasculitis and/or pneumonitis showed significantly higher levels of sICAM-1 than those without vasculitis or pneumonitis. Significant correlations were demonstrated between sICAM-1 and the factors IgG-RF, IgM-RF, erythrocyte sedimentation rate (ESR) and TNF-α in sera of RA patients. In addition, it was noted that the levels of sICAM-1 in SF were as high as those in the sera of patients with RA.     

Levels of soluble ICAM-1 in atopic dermatitis A new marker for monitoring the clinical activity?

Levels of soluble intercellular adhesion molecule-1 (sICAM-1) were measured in sera from patients with an acute exacerbation of their atopic dermatitis (AD) ( n = 16) on admission to and discharge from our department of dermatology. At admission, the sICAM-1 levels in sera from patients with AD were slightly higher than those of the blood donors ( n = 100) and dropped at discharge significantly ( P = 0.014) after improvement of the skin conditions. Therefore, sICAM-1 may be, together with soluble interleukin-2 receptor (sIL-2), eosinophilic cationic protein (ECP), and CD14, another marker for monitoring AD.     

支气管哮喘患者粘附分子和细胞因子的变化及其意义

目的:探讨支气管哮喘患者外周血白细胞粘附分子β2整合素(β2-integrin熏CD18)、血清可溶性细胞间粘附分子-1(sICAM-1,CD54)、白细胞介素-6(IL-6)和白细胞介素-8(IL-8)的变化及其意义。方法:采用流式细胞仪技术检测外周血白细胞CD18和血清sICAM-1的表达;采用酶连接免疫吸附方法(ELISA)检测血清IL-6和IL-8水平。结果:(1)与正常对照组相比,支气管哮喘患者外周血白细胞CD18和血清sICAM-1表达显著增加穴P<0.05雪;(2)与正常对照组相比,支气管哮喘患者血清IL-6和IL-8水平显著增加穴P<0.05雪;(3)支气管哮喘患者外周血白细胞CD18和血清sICAM-1表达呈显著正相关(r=0.791熏P<0.05)。结论:支气管哮喘患者外周血白细胞CD18和血清sICAM-1表达以及IL-6和IL-8水平增加,可能是支气管哮喘重要的发病机制之一。     

A study of serum immunoglobulins including IgE and reaginic antibodies in patients with bronchial asthma in relation to the spectrum of the disease

Immunoglobulins G, A, M, D, and E were studied in the sera obtained from sixty-nine bronchial asthma patients, who were graded objectively according to atopic score. Among other associated atopic diseases, they often had allergic rhinitis. Ninety-one per cent of these patients had elevated serum IgE levels and the mean level of serum IgE was more than 3.5 times higher than that observed in the normal subjects. Moreover, as their atopic score increased, the serum IgE levels were also elevated, and every patient with high atopic score, had elevated serum IgE levels: This indicates the association of atopic state with serum IgE level. Furthermore, reaginic antibodies were studied in some of these patients by intradermal tests, Prausnitz-Küstner (PK) reaction, conjunctival and bronchial provocation tests. Intradermal and PK tests were comparable and proved to be the most sensitive method of detecting reagins. The intensity of these reactions correlated significantly with serum IgE level, although this relationship is not invariably present. The reaginic activities in the sera of the patients with atopic bronchial asthma also compared well with the positive bronchial test (induced asthma) by inhalation of specific aerosol although this association is also not always present. Eleven patients with high atopic score had isolated serum IgA deficiency. There was a significant rise of mean serum IgM in comparison to the controls.     

Plasma prostaglandin levels in bronchial asthmatic patients measured by the 9-anthryldiazomethane-high performance liquid chromatography method

To evaluate some of the pathologic roles of prostaglandins (PGs) in bronchial asthma, plasma PGs levels in bronchial asthmatic patients were measured by the 9-anthryldiazomethane-HPLC method. Plasma TXB2 levels from stable bronchial asthmatic patients were higher than those from healthy subjects. Plasma PGF2 alpha levels were more elevated in atopic patients than in non-atopic ones. Plasma PGF2 alpha levels were more elevated in patients who suffered from attacks than in those who did not and plasma 6-keto PGF1 alpha levels were lower in patients who suffered from attacks than in those who did not. There was no significant difference in plasma TXB2 and PGs levels between mild and moderate asthmatic subjects. In the patients with mild attacks, aminophylline injection showed no significant effect on plasma TXB2 and PGs levels before and after the injection. These results suggest some of the roles of PGs in the pathogenesis of bronchial asthma.     

Different serum soluble Fas levels in patients with allergic rhinitis and bronchial asthma

BACKGROUND: The pathogeneses of allergic rhinitis and bronchial asthma are believed to be closely mutually related because of the similar dynamics of allergy-inducing cells and molecules and clinical overlap. In this study, we compared these diseases in the dynamics of cell apoptosis-regulating molecules. METHODS: Allergic rhinitis patients (n=36), bronchial asthma patients (n=22), and healthy subjects (n=32) were subjected to measurement of serum (soluble Fas) (sFas) levels during the stable and attack disease phases by a sandwich enzyme-linked immunosorbent assay. RESULTS: Serum sFas levels in patients with allergic rhinitis during the attack phase were significantly lower (P<0.0001) than those in healthy individuals. There were no differences between them during the attack and stable disease phases. In contrast, serum sFas levels in patients with bronchial asthma during the attack phase were higher (P<0.0005) than those in healthy individuals. Interestingly, the levels during the attack phase were lower (P<0.002) than those during the stable phase. CONCLUSIONS: Our results suggest a different pathogenesis for allergic rhinitis and bronchial asthma at the cell apoptosis-linked step.     

Soluble intercellular adhesion molecules in human schistosomiasis: correlations with disease severity and decreased responsiveness to egg antigens.

Granuloma formation, the principal pathologic consequence of infection with Schistosoma mansoni, is a complex process involving intricate cell-cell interactions in which intercellular adhesion molecules are likely to participate. To examine this possibility, sera of schistosomiasis patients in various clinical groups were assayed for the presence of soluble intercellular adhesion molecule 1 (sICAM-1) and soluble E-selectin (sE-selectin). Comparisons were made between groups with different infection intensities (as predicted by fecal egg count) as well as between groups with severe (hepatosplenic) or milder (intestinal) pathology. All groups had elevated levels of sICAM-1 compared with controls. Also, patients in the high egg-excreting and hepatosplenic groups had significantly higher levels of serum sICAM-1 than patients in the low-egg-excreting and intestinal groups, respectively. The levels of sE-selectin were significantly elevated in the sera of all patients except those in the hepatosplenic group compared with controls. Patients in the intestinal group had significantly higher levels of sE-selectin in their sera than did hepatosplenic group patients, but serum sE-selectin levels of high- and low-egg-excreting patients were comparable. A striking finding of this study was the inverse correlation observed between sICAM-1 levels and peripheral blood mononuclear cell responses to schistosome soluble egg antigens (SEA) but not with responses to other schistosome antigens, purified protein derivative, or mitogen. Because ICAM-1 can perform a costimulatory function in antigen-presenting cell-T cell interactions, it is possible that shedding of ICAM-1 in the granuloma microenvironment interrupts proper costimulation, leading to unresponsive SEA-specific T cells. In this way, sICAM-1 could be one factor contributing to the observed modulation of cellular responses to SEA in chronic human schistosomiasis.     

IgG, IgA, and IgM antibodies to mite in sera and sputa from asthmatic patients

In order to examine roles of antibodies to allergens in bronchial secretions, IgG, IgA, and IgM antibodies to mite in sputa from mite-sensitive asthmatics were measured by ELISA and compared with antibodies in sera. IgA antibodies to mite in sputa were significantly higher in mite-sensitive patients than in normal controls or mite-unsensitive asthmatic patients (P less than .01), whereas IgG and IgA antibodies in sera were significantly higher in mite-sensitive patients than in the other two groups (P less than .01). There were no significant differences of serum or sputum IgM antibodies among the three groups. The relative ratio of the level of IgA antibodies: the level of IgG antibodies was higher in sputum than in sera. IgA antibodies in bronchial secretions may play a protective role for asthma when allergens enter into the bronchial trees.     

Tests for bronchial asthma

One characteristic feature of bronchial asthma is an allergic inflammation of the airways involving eosinophil activation. Since adhesion molecules, cytokines, and chemokines play a critical role in eosinophil infiltration into the tissues, it is of paramount importance to utilize these inflammation-related factors as clinical parameters to assess the status of asthma. For this reason, we measured the level of RANTES and soluble ICAM-1 in patients with asthma. The concentration of plasma RANTES was significantly elevated in asthmatic patients as compared with normal subjects. Patients with asthma attacks exhibited higher RANTES levels than those in remission. sICAM-1 concentration was also higher in serum and sputum in patients with asthma than in healthy subjects. In order to detect eosinophil activation directly, we studied intracellular EG2 expression in eosinophils using whole-blood flow-cytometric analysis. The number of EG2-positive eosinophils was significantly greater in patients with attacks than in asymptomatic subjects. We measured the temperature of expiratory flow and temperature flux as an alternative approach to assess airway inflammation. This study was based on a concept that inflammation would produce heat resulting in the higher temperature. The coefficient of temperature flux was significantly greater in asthmatic patients than in normal controls. Therefore, these new tests may be useful for the evaluation and treatment of allergic inflammation in asthma.     

Soluble ICAM-1 as a regulator of nasal allergic reaction under natural allergen provocation

Background: Intercellular adhesion molecule-1 (ICAM-1) plays a key role in the early stage of the signal cascade leading to cellular extravasation and the development of an inflammatory response. Recently, it has been reported that the soluble form of this adhesion molecule is present in human sera, possibly mediating biological actions.
Objective: The purpose of this study was to investigate levels of soluble ICAM-1 (sICAM-1) and its receptors in patients with allergic rhinitis, and to discuss sICAM-1's biological function.
Methods: The levels of sICAM-1 in sera and nasal epithelial lining fluids (ELF), the percentage of CD11a-positive lymphocytes in the peripheral blood, and scores of subjective symptoms from 14 patients with pollinosis (allergic group) were measured from pre- to post-season, results were compared with those from 10 non-allergic subjects (control group).
Results: The levels of sICAM-1 in sera and ELF were upregulated, and CD11a-positive lymphocytes were downregulatcd during the in-season in the allergic group. In addition, levels of sICAM-1 in sera from the allergic group remained high during the post-season, when levels of other parameters (symptoms, blood eosinophil counts, sICAM-1 in ELF and CD11a-positive lymphocytes) had roughly returned to the initial pre-season levels.
Conclusions: We demonstrate systemic and local upregulation of sICAM-1 and systemic downregulation of LFA-1 positive lymphocytes in patients with seasonal allergic rhinitis under natural allergen provocation, suggesting that sICAM-1 plays a role in regulating seasonal allergic inflammation.     

A randomized, double-blind trial of the effect of treatment with montelukast on bronchial hyperresponsiveness and serum eosinophilic cationic protein (ECP), soluble interleukin 2 receptor (sIL-2R), IL-4, and soluble intercellular adhesion molecule 1 (sICAM-1) in children with asthma

BACKGROUND: Anti-inflammatory properties of leukotriene modifiers and their effect on bronchial hyperresponsiveness have not been studied in children with asthma. OBJECTIVE: The primary objective of this study was to determine the changes in serum levels of inflammatory mediators, clinical efficacy, and bronchial hyperresponsiveness after treatment with montelukast. METHODS: In this double-blind, randomized, placebo-controlled trial, 39 children with mild-to-moderate atopic asthma were randomly allocated to receive montelukast or placebo for 6 weeks. Main outcome measures were changes in serum concentrations of soluble interleukin 2 receptor (sIL-2R), IL-4, and soluble intercellular adhesion molecule 1 (sICAM-1); peripheral blood eosinophil count; and eosinophilic cationic protein (ECP). Asthma severity score, FEV(1), and bronchial hyperreactivity (BHR) for histamine were secondary end points. RESULTS: Compared to placebo, serum concentrations of IL-4, sICAM-1, and ECP and eosinophil blood counts significantly decreased after 6 weeks of treatment with montelukast. Montelukast significantly improved asthma control and FEV(1). Montelukast resulted in within-group significant decrease in levels of serum sIL-2R (611 vs. 483 pg/mL), IL-4 (0.123 vs 0.102 pg/mL), sICAM-1 (280 vs. 244 ng/mL), and ECP (74 vs. 59 microg/mL) and in eosinophil blood counts (349 vs. 310 cells/mm(3)). Mean FEV(1) value changed from 85% of predicted to 95% (P <.001) and for histamine (PC(20)H) from 2.8 mg/mL to 3.8 mg/mL (P <.001) after treatment with montelukast. There was no significant difference between montelukast and placebo recipients in the serum concentrations of sIL-2R and PC(20)H after treatment. CONCLUSION: Montelukast provides clinical benefit to patients with chronic asthma and decreases bronchial hyperresponsiveness. Montelukast caused a statistically significant decrease of serum concentrations in cytokine, ICAM-1, and ECP and peripheral blood eosinophil counts over the 6-week treatment period. This observation raises the possibility that leukotriene receptor antagonists, such as montelukast, may have effects on parameters of asthmatic inflammation.     

SECA, a new mediator of the human eosinophil response.

Spontaneous eosinophilic chemotactic activity (SECA) present in human sera can mediate the directed movement of normal human eosinophils. Our data utilize normal peripheral blood eosinophils obtained from subjects with 500 eosinophils/m3 or less. SECA is defined as that chemotactic activity for eosinophils present in serum that has been heat-inactivated immediately after collection. It was demonstrated in patients with severe chronic eczema with eosinophilia (20 to 30%); mixed collagen vascular disease with vasculitis; clinical serum sickness; acute glomerulonephritis, and chronic membranoproliferative glomerulonephritis. Control sera were obtained from normal, healthy individuals. The data indicated: (1) that SECA in patient sera was significantly higher than in control sera; (2) when activated by endotoxin, no additional chemotactic activity was generated from patient sera over that spontaneously present--by contrast, addition of endotoxin to control sera did result in increased chemotactic activity; (3) sera from patients with extrinsic bronchial asthma had no SECA.     

支气管哮喘患儿治疗前后血清CGRP、MMP-9和TIMP-1检测的临床意义

目的:探讨了支气管哮喘患儿治疗前后血清CGRP、MMP-9和TIMP-1水平的变化及临床意义.方法:应用放射免疫分析和酶联法对32例支气管哮喘患儿进行了治疗前后血清CGRP、MMP-9和TIMP-1检测,并与35名正常健康儿作比较.结果:在治疗前支气管哮喘患儿血清CGRP水平非常显著地低于正常儿组(P<0.01),而M...     

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.     

Soluble intercellular adhesion molecule-1 (sICAM-1) in sera of patients with Graves' ophthalmopathy and thyroid diseases.

Intercellular adhesion molecule, a ligand for the leucocyte integrins CD11a/CD18 (LFA-1) and CD11b/CD18 (Mac-1), that plays an important role in a variety of inflammatory and immune-mediated mechanisms, is strongly expressed in retroocular connective tissue from patients with Graves' ophthalmopathy (GO) and involved in lymphocyte attachment to cultured retroocular fibroblasts via the ICAM-1/LFA-1-mediated pathway. Here, we report the detection and functional activity of a soluble form of the ICAM-1 molecule (sICAM-1) in sera from patients with GO and other thyroid diseases. Serum concentrations for sICAM-1 were determined using a highly sensitive ELISA. Compared with normal controls, patients with hyperthyroid or euthyroid GO and patients with Riedel's invasive fibrous thyroiditis revealed markedly elevated sICAM-1 serum concentrations (all P < 0.0001). In patients with Graves' disease (GD) without clinical GO and in patients with Hashimoto's thyroiditis (HT), sICAM-1 levels were elevated to a lesser degree (both P < 0.001). sICAM-1 serum levels in patients with non-autoimmune hyperthyroidism due to a toxic adenoma were not significantly different from normal controls. In a separate group of 12 patients with severe inflammatory GO, sICAM-1 serum levels markedly declined (P < 0.0001) within 3 months of glucocorticoid therapy in nine patients who responded to this form of treatment with a decrease in periorbital inflammation. In contrast, sICAM-1 serum levels remained unchanged in three patients with poor response to steroids and persistent inflammatory periorbital disease. When tested in a cell adhesion assay, GO sera containing elevated concentrations of sICAM-1 were found to enhance the attachment of peripheral blood mononuclear cells (PBMC) to interferon-gamma (IFN-gamma)-treated retroocular fibroblasts in a dose-dependent manner, up to a maximal stimulation of approximately 5.5-fold (P < 0.001). This effect was abolished by preabsorption of sera with a MoAb against ICAM-1 and inhibited, in a dose-dependent manner, by coincubation with increasing concentrations of purified sICAM-1. In conclusion, sICAM-1 concentrations are markedly elevated in sera from patients with GO, and changes in sICAM-1 serum levels during glucocorticoid therapy closely parallel changes in the degree of inflammation. Given the capacity of sICAM-1 to modulate the adhesion of lymphocytes to retroocular fibroblasts in vitro, sICAM-1 may play a role in the ongoing immune process within the connective tissue in GO.