Soluble adhesion molecules in serum throughout the menstrual cycle

BACKGROUND: The female reproductive and immune systems are integrally linked with respect to shared cellular and molecular mediators. Cell adhesion molecules (CAMs) involved in leukocyte-endothelial interactions, e.g. intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin, are regulated by sex steroids when expressed by cultured endothelium, while uterine and ovarian CAM expression appears to be cyclically or gonadotrophin-regulated. METHODS AND RESULTS: To determine if these effects translate into changes in soluble CAMs (sICAM-1, sVCAM-1 and sE-selectin) levels in peripheral blood, normally cycling women received regular venous sampling throughout a complete menstrual cycle. Soluble ICAM-1 levels were maximal in the early and mid-follicular stages, progressively decreased throughout the remainder of the cycle and were significantly reduced in the late luteal stage (P < 0.001). Levels of sVCAM-1 fluctuated during the follicular phase and mid-cycle, but also declined in the late luteal phase (P < 0.01), whereas sE-selectin concentration did not vary markedly across the menstrual cycle. Plasma hormone and urinary hormone metabolite levels confirmed precise cycle tracking and revealed an inverse relationship between sICAM-1 and estradiol (r = -0.38, P < 0.005). A negative correlation was also apparent between sVCAM-1 and circulating monocyte cell numbers (r = -0.47, P < 0.001). CONCLUSIONS: The normal cyclic variation in peripheral sICAM-1 and sVCAM-1 levels reported here may reflect uterine and/or ovarian tissue remodelling events, and is of particular importance if soluble CAM levels are utilized as biological markers of certain disease states in women of reproductive age.     

Soluble endothelium-associated adhesion molecules in patients with Graves' disease.

The targeting and recruitment of inflammatory cells to vascular endothelium in Graves' disease (GD) is mediated by intercellular adhesion molecule-1 (ICAM-1), endothelial leucocyte adhesion molecule-1 (ELAM-1), and vascular cell adhesion molecule-1 (VCAM-1). We have studied serum levels of soluble ICAM-1 (sICAM-1), soluble ELAM-1 (sELAM-1), and soluble VCAM-1 (sVCAM-1) in patients with GD (n = 21) and in patients with iodine-deficient goitre (IDG) (n = 23). The serum levels of sICAM-1 were markedly elevated in patients with GD before treatment with thiamazole (median 560 ng/ml versus 185 ng/ml in patients with IDG). In addition, elevated serum concentrations of sELAM-1 (median 85 ng/ml versus 33 ng/ml, respectively) and sVCAM-1 (median 42 ng/ml versus 15 ng/ml, respectively) were observed in patients with GD (P < 0.01 for all). The serum levels of sELAM-1 and sVCAM-1 dropped significantly after initiation of therapy and were within the normal range after 4, and 8 weeks of therapy, respectively. Serum levels of sICAM-1 were elevated even after 8 weeks of therapy. Serum levels of sVACM-1 and sICAM-1 correlated with the serum concentrations of anti-thyroid-stimulating hormone (TSH)-receptor antibodies (TSHR-R) (n = 21; r = 0.929 and r = 0.810, respectively) and anti-thyroid peroxidase antibodies (TPO-Ab) (n = 21; r = 0.673 and r = 0.750, respectively). However, no correlation between sELAM-1 and TPO-Ab, TSHR-R, and anti-thyroglobulin antibodies (Tg-Ab), respectively, could be found. In addition to thyroid hormones and autoantibodies, serum concentrations of sELAM-1 and sVCAM-1, but not sICAM-1, could be useful as clinical markers for disease activity.     

Maternal serum levels of VCAM-1, ICAM-1 and E-selectin in preeclampsia

Endothelial dysfunction is thought to be a central pathogenic feature in preeclampsia on the basis of elevated adhesion molecules. The aim of the present study was to compare the levels of soluble vascular cell adhesion molecule-1 (sVCAM-1), intercellular adhesion molecule-1 (sICAM-1) and E-selectin (sE-selectin) in sera of normal and preeclamptic pregnancies. We studied the serum levels of sVCAM-1, sICAM-1 and sE-selectin in normal pregnant women (n=63), mild preeclampsia (n=33) and severe preeclampsia (n=82). Concentrations of soluble adhesion molecules were determined with enzyme-linked immunoassay (ELISA). Serum concentrations of sVCAM-1 were significantly higher in both mild (p=0.004) and severe preeclampsia (p=0.000) than normal pregnancy. There were also significant differences in sVCAM- 1 levels between mild and severe preeclampsia (p=0.002). sICAM-1 levels of severe preeclampsia were statistically different from those of normal pregnancy (p=0.038). Levels of sE-selectin were elevated in both mild (p=0.011) and severe preeclampsia (p=0.000) compared to normal pregnancy, but no statistical difference between the mild and severe preeclampsia (p=0.345). These results suggest that all three soluble adhesion molecules are increased in severe preeclampsia, and sVCAM-1 among them may be useful in predicting the severity of preeclampsia.     

Serum soluble adhesion molecules (sICAM-1, sVCAM-1, sE-selectin) and neopterin in patients with Sjögren's syndrome

Sj?gren's syndrome is a systemic autoimmune disease characterized by focal lymphocytic infiltration of the salivary and lacrimal glands. Expression and up-regulation of adhesion molecules and activation of cellular immune system is essential for the migration of inflammatory cells into tissues. Soluble forms of adhesion molecules sICAM-1, sVCAM-1, sE-selectin and neopterin were analyzed in serum of 17 patients with primary Sj?gren's syndrome and 11 patients with secondary Sj?gren's syndrome together with 26 age-matched healthy blood donors. There were significantly higher serum concentrations (mean +/- 1SD) of sICAM-1 (362.0 +/- 67.9 ng/ml, p < 0.001), sE-selectin (78.7 +/- 28.1 ng/ml, p < 0.001) and neopterin (17.9 +/- 6.4 nmol/l, p < 0.001) in primary Sj?gren's syndrome patients in comparison to control group (sICAM-1: 128.3 +/- 46.9 ng/ml, sE-selectin: 46.3 +/- 39.5 ng/ml, and neopterin: 7.6 +/- 2.3 nmol/l). Sera from patients with secondary Sj?gren's disease contained significantly higher levels of sICAM-1 (356.0 +/- 62.4 ng/ml, p < 0.001), sE-selectin (65.5 +/- 27.0 ng/ml, p < 0.05), and neopterin (18.8 +/- 9.8 nmol/l, p < 0.001) in comparison with control group. There were no significant differences between patients with primary and secondary Sj?gren's syndrome in any parameters tested. No statistically significant differences in serum levels of sVCAM-1 were found either in patients with primary or secondary SS compared to control group.     

Serum soluble adhesion molecules (sICAM-1, sVCAM-1 and sE-selectin) in healthy school aged children and adults

The aim of this study was to map normal levels of serum soluble isoforms of adhesion molecules in relation to age and sex in the group of school-aged children. sICAM-1, sVCAM-1 and sE-selectin were determined in the group of 158 normal children subdivided into two subgroups; 6-10 years (68 children, median age 8 years) and 11-15 years (90 children, median age 12 years) and in 70 normal adult blood donors (25 females and 45 males, median age 46 years). The levels of sICAM-1 and sE-selectin fell down significantly over the age range 6-15 years, while the level of sVCAM-1 was remained. Age-related normal ranges were established using correlation analysis and were expressed as the 5%-95% percentiles intervals: sICAM-1 206.8-486.8 ng/ml, sE-selectin 36.7-153.2 ng/ml in the group of 6-10 years old children, sICAM-1 184.1-354.0 ng/ml, sE-selectin 29.9-114.1 ng/ml in group of 11-15 years old children. The levels of sVCAM-1 were 359.6-822.0 ng/ml and were constant within the examined age interval from 6 to 15 years. The influence of sex was also assayed and it was not statistically significant in any age category tested. Normal ranges of sICAM-1 (60.2-218.4 ng/ml), sE-selectin (8.3-116.9 ng/ml) and sVCAM-1 (338.0-1148.0 ng/ml) were established for adult population of healthy blood donors using the same methods.     

Differential up-regulation of circulating soluble selectins and endothelial adhesion molecules in Sicilian patients with Boutonneuse fever.

In 150 patients with Boutonneuse fever (BF), caused by Rickettsia conorii, we studied the plasma levels of soluble L-selectin (sL-selectin), vascular cell adhesion molecule-1 (sVCAM-1), intercellular adhesion molecule-1 (sICAM-1) and E-selectin (sE-selectin) in various phases of disease to clarify their role in disease evolution. Results indicate that during the acute phase of BF there is a significant increase in the serum levels of sL-selectin, sE-selectin, sVCAM-1 and sICAM-1. sL-selectin and sVCAM-1 returned to normal levels in the third week of disease, whereas sE-selectin and sICAM-1 persisted at significantly high levels even after the third week. The secretion of these soluble CAMs in BF is mainly the result of leucocyte expression and endothelial cell activation, but secretion also appears to mediate anti-inflammatory activities, moderating leucocyte adhesion and reducing in particular lymphocyte and monocyte infiltration. Only sL-selectin serum levels were found to correlate with the acute phase of infection characterized by fever.     

Levels of soluble VCAM-1, soluble ICAM-1, and soluble E-selectin during disease exacerbations in patients with systemic lupus erythematosus (SLE); a long term prospective study.

Active SLE is characterized by immune deposits and subsequent vascular inflammation in many organs. Expression and up-regulation of adhesion molecules is basic to migration of inflammatory cells into the tissues. Recently, soluble isoforms of these molecules have been described which might be an expression of their up-regulation in the tissues and, as such, of disease activity. The purpose of this study was to evaluate whether changes in levels of soluble adhesion molecules reflect disease activity. We analysed serial sera in a 6-month period preceding 22 consecutive exacerbations of SLE for levels of soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), and sE-selectin. Levels were related to clinical disease activity (SLEDAI), and levels of anti-dsDNA and complement. At the time of maximal disease activity, levels of sVCAM-1 in patients with SLE were higher than those in controls (P < 0.0001), levels in patients with renal involvement being higher than in those without (P < 0.02). Levels of sVCAM-1 correlated with SLEDAI scores (P < 0.05) and, inversely, with levels of C3 (P = 0.01). In addition, in the presence of anti-dsDNA, levels of sVCAM-1 tended to correlate with levels of these autoantibodies (P < 0.1). Levels of sICAM-1 were normal and sE-selectin levels even decreased compared with controls. Levels of sVCAM-1 were higher at the moment of relapse (P = 0.001) than at 6 months before this time point. This rise correlated with the rise in SLEDAI score (P < 0.02). Levels of sICAM-1 and sE-selectin did not rise, and remained in the normal range in all exacerbations studied. In conclusion, in contrast to sICAM-1 and sE-selectin, levels of sVCAM-1 are increased, rise parallel to disease activity during exacerbations in SLE, and are associated with decreasing levels of complement factors. This favours the hypothesis of immune deposit formation, activation of the complement cascade and activation of endothelial cells. Concurrent up-regulation of vascular adhesion molecules may thus result in transmigration of activated inflammatory cells inducing tissue damage.     

Do Soluble Cell Adhesion Molecules Play a Role in Endometriosis?

PROBLEM: Endometriosis is a chronic inflammatory disease associated with diverse immunologic disturbances. Cell adhesion molecules are essential for the development of immune and inflammatory reactions. This study was conducted to investigate whether or not serum and peritoneal levels of soluble cell adhesion molecules are altered in women with endometriosis. METHOD OF STUDY: The study group comprised five women with moderate-to-severe endometriosis. Eight healthy women with a normal diagnostic laparoscopy served as controls. Serum and peritoneal fluid samples from both groups were analyzed for the soluble isoform of intercellular cell adhesion molecule-1 (sICAM-1). vascular cell adhesion molecule-1 (sVCAM-1), endothelial selectin (sES), and platelet selectin (sPS). RESULTS: Serum levels of sICAM-1 were significantly increased in women with endometriosis (median levels: 410.4 ng/mL; range: 233.9 ng/mL 598.4 ng/mL vs. 235.7 ng/mL; range: 187.4 ng/mL -323.7 ng/mL; P = 0.02). Although the levels of sVCAM-1, sES, and sPS in both samples were higher in the study group, the differences did not reach significance. CONCLUSIONS: Our results suggest a role of ICAM-1 in the pathophysiology of endometriosis. However. the role of other investigated cell adhesion molecules should be confirmed by further studies.     

Microplate ELISAs for soluble VCAM-1 and ICAM-1

Soluble vascular cell adhesion molecule (sVCAM-1) and soluble intercellular adhesion molecule (sICAM-1) are adhesion molecules that are detectable in the serum of patients with cancer, cardiovascular diseases (CVD), and type 2 diabetes. This report describes enzyme-linked immunosorbent assays (ELISAs) on microplates for sVCAM-1 and sICAM-1. The ELISAs have the sandwich test format; polyclonal antibodies are coated on microwells and a one-step procedure is used in which the serum specimen and detecting antibody are added simultaneously to an antibody-coated well. These assays both use HRP-conjugated sheep anti-mouse-IgG to generate the color for quantification. Sensitivities for detecting sVCAM-1 and sICAM-1 are 49 and 40 ng/ml, respectively. Coefficients of variation for within-day and day-to-day replicate analyses are <10%. Results by these in-house ELISAs for serum sVCAM-1 and sICAM-1 compared well with those obtained with commercial kits from R&D Systems, Inc. (correlation coefficients = 0.98 and 0.99 for sVCAM-1 and sICAM-1, respectively). Reference values for serum sVCAM-1 and sICAM-1 levels were measured in 369 apparently healthy Chinese adults, age 30 to 79 yr. There was no significant effect of gender on the reference values for sVCAM-1 or sICAM-1. Serum sVCAM-1 levels (mean +/- SD) were higher in subjects 60 yr old (625 +/- 126 ng/ml), compared to those <60 yr old (525 +/- 110 ng/ml) (p <0.001). Age did not significantly affect the reference values for serum sICAM-1 levels (mean +/- SD, 249 +/- 86 ng/ml). The authors believe that these simple, inexpensive ELISAs will be useful for assessing the risks for development of cancer, CVD, and type 2 diabetes.     

Changes in circulating levels of soluble cell adhesion molecules following highly active antiretroviral treatment of HIV-1-infected patients

Increased levels of soluble cell adhesion molecules (sCAM) have been reported in HIV-1 infection and may possibly contribute to altering the adhesion mechanisms of phagocytic cells. We evaluated the effect of highly active antiretroviral therapy (HAART) on plasma levels of sL-selectin, sE-selectin, intercellular cell adhesion molecule-1 (sICAM-1), sICAM-3, and vascular cell adhesion molecule-1 (sVCAM-1). Study participants included 22 HIV-1-infected patients with a CD4+ T-cell count/microl below 500 who were started on a HAART regimen and followed up for 9 months. After the initiation of therapy, plasma sL-selectin concentrations progressively decreased to normal ranges in the majority of our patients (P < 0.001), while no changes in sE-selectin were found. In all patients sICAM-1 remained relatively constant at significantly elevated concentrations during the 9 months of therapy. A significant reduction in plasma concentrations of both sICAM-3 and sVCAM-1 was found; however, the levels of these sCAM were not normalized by HAART and remained significantly elevated throughout the study (P < 0.001). The reduced release of sL-selectin could improve the ability of phagocitic cells to migrate in response to chemotactic stimuli after starting HAART. On the other hand, the persistent elevation of sICAM-1, sICAM-3, and sVCAM-1 could reflect continuous HIV-1-mediated immune activation, despite adequate control of plasma HIV-1 replication by therapy.     

Levels of intracellular adhesion molecule-1 and vascular cell adhesion molecule-1 in children with Henoch-Sch?nlein purpura.

BACKGROUND AND PURPOSE: Henoch-Sch?nlein purpura (HSP) is a small vessel vasculitis. Soluble adhesion molecules play a very important role in the immuno-inflammatory reaction of damaged vascular tissues. This study investigated the prognostic and diagnostic potential of soluble intracellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1) in HSP. METHODS: Serum levels of sICAM-1 and sVCAM-1 were studied in 26 children with HSP. Paired blood samples (during acute and convalescent stages) were collected from 17 of the children and assayed by enzyme-linked immunosorbent assay. Correlations with clinical manifestations were examined. Seventeen healthy children served as controls. RESULTS: Both sICAM-1 and sVCAM-1 were significantly elevated at the acute stage compared with the remission stage of HSP patients versus controls (p=0.006 and p=0.0173, respectively). CONCLUSIONS: Although the levels of sICAM-1 and sVCAM-1 were not correlated with the severity of clinical manifestations in HSP, these soluble adhesion molecules may serve as diagnostic markers.     

Changes in plasma levels of adhesion molecules after percutaneous mitral balloon valvuloplasty.

BACKGROUND: Adhesion molecules are expressed on vascular endothelium and on immune and inflammatory cells. Recently increased levels of adhesion molecules have been shown in patients with rheumatic mitral stenosis. This study examined the serum levels of the adhesion molecules intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and E-selectin in patients with rheumatic mitral stenosis and the effects of percutaneous mitral balloon valvuloplasty (PMBV) on these adhesion molecules. MATERIALS AND METHODS: Thirty five patients (3 men, 32 women, mean age 39+/-5 years) with severe rheumatic mitral stenosis who underwent percutaneous balloon mitral valvuloplasty, and 35 age and sex matched healthy control subjects were included in the study. Serum levels of ICAM-1, VCAM-1, and E-selectin were measured in all patients who underwent PMBV and in all control subjects. Blood samples were taken for measurement of adhesion molecules immediately before and 24 h after the mitral balloon valvuloplasty. RESULTS: The plasma levels of soluble adhesion molecules E-selectin, ICAM-1 and VCAM-1 were significantly elevated in patients with mitral stenosis compared to control subjects: E-selectin, 97+/-59 vs. 45+/-24 ng/ml (P=.001), sICAM-1, 874+/-301 ng/ml vs. 238+/-82 ng/ml (P<.0001); sVCAM-1, 3056+/-763 ng/ml vs. 985+/-298 ng/ml (P<.0001). Plasma levels of VCAM-1 significantly increased 24 h after the valvuloplasty procedure (3056+/-763 ng/ml vs. 3570+/-1225 ng/ml P=.013). Plasma levels of E-selectin showed a significant decrease after PMBV (97+/-59 vs. 70+/-58 ng/ml, P=.043) and plasma levels of ICAM-1 did not show any change after PMBV (874+/-301 vs. 944+/-377 ng/ml, P=.356). CONCLUSION: Cellular adhesion molecules, sICAM-1, E-selectin, sVCAM-1 have shown changes in different directions in response to PMBV. These results necessitate further studies to clarify the mechanism underlying the association between adhesion molecules and PMBV as well as rheumatic mitral stenosis.     

Increase in adhesion molecules in cerebrospinal fluid of children with mumps and mumps meningitis

Adhesion molecules play a key role in leucocyte migration into the central nervous system (CNS). Concentrations of endothelial-derived soluble intercellular adhesion molecule-1 (sICAM-1) and leucocyte-originated soluble L-selectin (sL-selectin) in cerebrospinal fluid (CSF) of children with mumps meningitis (mononuclear pleocytosis, n = 33) and mumps (absence of pleocytosis, n = 9) were compared with values from age-matched control group (n = 19). In 14 patients from the meningitis group, adhesion molecule levels together with albumin concentration were estimated in paired CSF/serum samples to calculate concentration quotients and determine molecule intrathecal release. Both sICAM-1 (median 3.44 versus 0.86 ng/ml; P < 0.0001) and sL-selectin (median 29.91 versus 8.52 ng/ml; P < 0.0001) concentrations in CSF were increased in mumps meningitis patients compared with controls. Increased levels of the selected adhesion molecules were also observed in mumps patients without CNS involvement when compared with controls (median sICAM-1: 1.14 versus 0.86 ng/ml, sL-selectin: 13.54 versus 8.52 ng/ml; P < 0.01). Additionally, the concentration of adhesion molecules was found to correlate with CSF leucocyte count. Considerable correlation of sICAM-1 and sL-selectin quotients and corresponding albumin quotients suggests that a majority of the soluble adhesion molecules originated from the bloodstream. Analysis of adhesion molecule levels demonstrated indirect evidence of brain-derived fractions. Our results suggest the involvement of adhesion molecules during the early phase of mumps meningitis.     

Blood serum levels of vascular cell adhesion molecule (sVCAM-1), intercellular adhesion molecule (sICAM-1) and endothelial leucocyte adhesion molecule-1 (ELAM-1) in diabetic retinopathy

BACKGROUND: Interaction between cells via intimate cell-cell contact is facilitated by a cell surface molecules, termed adhesion molecules. The aim of the study was to evaluate the blood serum concentration of soluble forms of vascular cell adhesion molecule (VCAM-1), intercellular adhesion molecule (ICAM-1) and endothelial leukocyte adhesion molecule-1 (ELAM-1) in patients with type 1 diabetes mellitus without and with diabetic retinopathy. MATERIALS AND METHODS: The study was performed in 75 patients with type 1 diabetes mellitus, 35 without retinopathy (group 1) and 40 with retinopathy (group 2). Soluble forms of VCAM-1, ICAM-1 and ELAM-1 were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: The serum concentration of sICAM-1 and sELAM-1 were significantly elevated and the concentration sVCAM-1 was elevated but not significantly in diabetic patients when compared with control subjects. There was a significant difference in VCAM-1 concentrations between the control group and group 2 (965.9 +/- 229.0 vs. 1283.7 +/- 387.6 ng/ml, p < 0.05) and between group 1 and group 2 (1115.0 +/- 285.5 vs. 1283.7 +/- 387.6 ng/ml, p < 0.05). There were significant differences in sICAM-1 concentrations between the control group and group 1 (p < 0.05) and between the control group and group 2 (p < 0.05). Where was no significant difference in sICAM-1 concentration between group 1 and 2 (405.2 +/- 135.9 vs. 443.1 +/- 112.7 ng/ml, p = 0.08). ELAM-1 concentration was significantly elevated in group 2 (120.5 +/- 49.3 ng/ml) when compared with the control group (51.7 +/- 18.1 ng/ml, p < 0.005) and with group 1 (81.2 +/- 27.7 ng/ml, p < 0.05). CONCLUSIONS: The correlations found between sVCAM-1, sICAM-1 and sELAM-1 and the presence of retinopathy suggest that cellular adhesion and neovascularization may be linked processes.     

Soluble cell adhesion molecules and von Willebrand factor in children with Kawasaki disease.

Fifty-nine children with acute Kawasaki disease (KD), a childhood vasculitis, were compared with 35 children with fever due to infection and 48 healthy children. Levels of soluble E-selectin (sE-selectin), soluble intercellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1) in the healthy children were double those found in adults. All three soluble cell adhesion molecules and von Willebrand factor (vWF) were higher in the children with KD than in the healthy children, but only sE-selectin, a marker for activated endothelial cells, and sICAM-1 were higher than in the febrile children. The high levels of vWF in KD appear to reflect the prominent acute-phase reaction. This information can help us to understand further the complex interactions between cytokines, circulating inflammatory cells and the vascular endothelium, and may lead to new therapeutic avenues in KD and other inflammatory diseases and vasculitides.     

Increased plasma concentrations of sICAM-1, sVCAM-1 and sELAM-1 in patients with Plasmodium falciparum or P. vivax malaria and association with disease severity.

Increased serum concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), soluble endothelial leucocyte adhesion molecule-1 (sELAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) were detected in Danish malaria patients infected with sequestering Plasmodium falciparum or non-sequestering P. vivax parasites, as well as in patients with sepsis or meningitis. Levels of soluble adhesion molecules remained elevated in the P. falciparum patients for several weeks after initiation of treatment. Plasma concentrations of sICAM-1, sVCAM-1 and sELAM-1 were higher in Gambian children with severe P. falciparum malaria than in children with mild malaria. Plasma levels of sVCAM-1 and sELAM-1 were significantly correlated. Plasma levels of sELAM-1 and sVCAM-1 may reflect endothelial inflammatory reactions and these reactions may be harmful for humans infected with malaria parasites.     

妊娠期高血压病患者血管活性因子水平的变化

目的：探讨妊娠期高血压病患者血浆神经肽Y（NPY）、降钙素基因相关肽（CGRP）、可溶性血管细胞黏附分子-1（sVCAM-1）及可溶性细胞间黏附分子-1（sICAM-1）水平的变化与患者发病的关系。方法：：32例非孕妇女、30例正常孕妇（对照组）及30例妊娠期高血压病患者的血浆NPY、CGRP含量均采用放射免疫分析;血浆sVCAM-1和sICAM-1采用酶联免疫分析法测定。结果：本文结果显示,对照组CGRP水平较非孕妇女组升高显著（P〈0.05）;妊娠期高血压病治疗前组CGRP水平较对照组降低非常显著（P均〈0.01）;经治疗水平明显升高,但与对照组比较仍存在显著差异（P〈0.05）。NPY水平对照组较非孕妇女组升高无显著性（P〉0.05）;治疗前组NPY水平较对照组升高非常显著（P〈0.01）;经治疗水平已明显下降,与对照组比较差异无显著性（P〉0.05）。sVCAM-1水平对照组与非孕妇女组比较无显著性差异（P〉0.05）;治疗前组水平较对照组升高显著（P〈0.05）;经治疗水平明显下降,较对照组略高,但已无显著性差异（P〉0.05）。sICAM-1水平显示对照组及非孕妇女组略升高,但无显著性差异（P〉0.05）;治疗前组较对照组略高,但也无显著性差异（P〉0.05）;经治疗sICAM-1水平与对照组比较亦无显著性差异（P〉0.05）。相关分析结果显示,CGRP含量血浆浓度与其平均动脉压呈显著负相关（r=-0.5812,P〈0.01）,而NPY含量则显著高于对照组妇女,并随病情的加重而上升,与其平均动脉压呈显著正相关（r=0.6097,P〈0.01）。结论：妊娠期高血压病患者血浆NPY、CGRP及sVCAM-1三项指标的测定对于了解和认识其发病机理及预估病情有帮助。     

Differential dose-dependent effects of prednisolone on shedding of endothelial adhesion molecules during human endotoxemia

Low dose prednisolone was shown to be beneficial in the treatment of the Acute respiratory distress syndrome (ARDS) and septic shock. One corticosteroid-induced effect, postulated to mediate corticosteroid-induced anti-inflammatory effects, is decreased expression of adhesion molecules on endothelial cells, thereby preventing leukocyte recruitment at inflammatory sites. The current study aimed to investigate the effect of increasing doses of prednisolone on the release of soluble adhesion molecules in healthy volunteers challenged with endotoxin. Therefore, 32 healthy, male volunteers received prednisolone orally at doses of 0mg, 3mg, 10mg or 30 mg at 2h before injection of endotoxin prepared from Escherichia coli (4 ng/kg) and levels of soluble E-selectin (sE-selectin), soluble VCAM-1 (sVCAM-1) and soluble ICAM-1 (sICAM-1) were measured. Levels of all markers were increased after induction of endotoxemia. Levels of sE-selectin were inhibited by a dose of 3mg prednisolone and levels of sVCAM-1 were decreased after a dose of 10mg. Maximal inhibition of both sE-selectin and sVCAM-1 levels was achieved by the highest dose of prednisolone 30 mg. Remarkably, prednisolone 3mg potentiated endotoxin-induced sVCAM-1 release. Levels of sICAM-1 were not affected by prednisolone. Together, the data suggest that prednisolone differentially and dose-dependently influences the release of soluble endothelial adhesion molecules during human endotoxemia.     

Trophoblasts and soluble adhesion molecules in peripheral blood of women with pregnancy-induced hypertension

PROBLEM: The current hypothesis on the pathogenesis of pregnancy-induced hypertension (PIH) considers it as an endothelial disorder that is first local but with the potential of becoming general. The aim of the work was to investigate the relation of the number of trophoblast cells in maternal peripheral blood against the serum levels of soluble vascular and intercellular cell adhesion molecule (sVCAM-1 and sICAM-1) in PIH. METHOD OF STUDY: Women with PIH were at 28th to 40th week of gestation. Control group were normotensive (NT) pregnant women at 28th to 41st week of gestation. Flow cytometry was used to assess the relative number of the trophoblasts in the peripheral blood. Trophoblasts were labeled with monoclonal anti-human trophoblast protein antibody MCA 277. The presence of sVCAM-1 and sICAM-1 was determined using the enzyme-linked immunosorbent assay method. RESULTS: Women with PIH had significantly higher trophoblasts number than NT women (median 19.0, range 5.0-57.0/400 microL versus median 7.0, range 0.0-18.0/400 microL; P = 0.000011) as well as plasma level of sVCAM-1 when compared with NT women (median 730.0, range 325.0-1525.0 ng/mL versus median 493, range 310-1075 ng/mL; P = 0.02). ICAM-1 level in the PIH group was slightly elevated (median 280.0, range 174.0-524.0 ng/mL) when compared with NT women (median 260.0, range 190.0-464.0 ng/mL, P = 0.322). Eight of 21 women with PIH had proteinuria but no correlation was found between this symptom and the laboratory findings. CONCLUSION: The increased number of trophoblast cells in maternal peripheral blood and higher levels of sVCAM-1 correlate with the presence of PIH. The differences of sVCAM levels were significantly higher than those observed for sICAM. The results indicate an association between circulating trophoblasts and vascular endothelium activation, during PIH.     

Smoking and disease severity are independent determinants of serum adhesion molecule levels in Graves' ophthalmopathy

Adhesion molecules play a key role in autoimmune disorders, and serum concentrations of soluble adhesion molecules are increased in Graves' ophthalmopathy (GO). Whether this is due to the strong association with smoking is unknown. It is also not known if the severity or activity of GO determine the serum levels of adhesion molecules. We measured serum concentrations of sICAM-1, sVCAM-1 and sELAM-1 in 62 euthyroid Graves' patients with untreated GO, in 62 healthy controls matched for sex, age and smoking habits, and in 26 euthyroid Graves' patients without GO. GO severity was assessed by the Total Eye Score and the activity by the Clinical Activity Score. Adhesion molecules were measured by highly sensitive ELISAs. GO patients had higher levels than controls (median values in ng/ml with range): sICAM-1 300 [171--575] versus 244 [119--674], P < 0.001; sVCAM-1 457 [317--1060] versus 410 [238--562], P < 0.001; and sELAM-1 61 [19--174] versus 53 [23--118], P = 0.021. Euthyroid Graves' disease patients without GO had levels similar to controls: sICAM-1 273 138--453), sVCAM-1 386 [260--1041] and sELAM-1 46 [22--118]. Smoking had an independent effect and was associated with higher levels of sICAM-1 and lower levels of sVCAM-1 in both GO patients and controls; sELAM-1 levels were comparable. In the 62 GO patients, sICAM-1 correlated significantly with severity of eye disease (r = 0.40, P = 0.002). No correlation was found with the duration of GO, the Clinical Activity Score or TBII levels. Multivariate analysis of all 150 subjects showed that the presence of GO and smoking are independent determinants of sICAM-1 and sVCAM-1 concentrations. In GO patients, the Total Eye Score was a stronger determinant than smoking. It is concluded that (i) smoking is associated with increased sICAM-1 and decreased sVCAM-1 levels; (ii) independent from smoking, euthyroid GO patients have higher levels of sICAM-1, sVCAM-1 and sELAM-1 than patients with euthyroid Graves' disease or healthy controls; (iii) the major determinant of sICAM-1 in GO patients is the severity of their eye disease.