Keratinocyte expression of intercellular adhesion molecule 1 (ICAM-1) correlated with infiltration of lymphocyte function associated antigen 1 (LFA-1) positive cells in evolving allergic contact dermatitis reactions

Adhesion molecules are considered to have an important role in inflammatory reactions. We investigated the kinetics of ICAM-1 expression on keratinocytes and correlated this with the numbers of lymphocytes expressing LFA-1 in the dermis and epidermis of evolving allergic contact dermatitis reactions. In nickel-sensitive individuals, after application of a nickel patch, increased expression of ICAM-1 on keratinocytes was observed as early as 3 h and reached a maximum at 48 h. The number of lymphocytes expressing LFA-1 in the dermis and epidermis was greatest at 48 h. The LFA-1 cells were observed to be in close proximity to keratinocytes expressing ICAM-1, thus supporting the hypothesis that T-lymphocytes attach to keratinocytes via LFA-1/ICAM-1 molecules.     

Monitoring of disease activity by measurement of inflammatory markers in atopic dermatitis in childhood

Serum levels of soluble interleukin-2 receptor (sIL-2R), intercellular adhesion molecule-1 (ICAM-1), endothelial leukocyte adhesion molecule (ELAM-1), and eosinophil cationic protein (ECP) were measured in 20 patients with atopic dermatitis before and after 4 days'treatment with prednisolone p.o. as well as in 16 healthy, nonatopic controls. Before steroid treatment, patients with atopic dermatitis demonstrated significantly higher serum levels of sIL-2R, ICAM-1, and ECP than healthy controls (P<0.001), whereas ELAM-1 levels were not different between the groups. After 4 days of steroid treatment, clinical improvement was associated with a decrease of sIL-2R (P<0.003), ICAM-1 (P<0.004), and ECP serum levels (P<0.003), but ELAM-1 levels remained unchanged. Both serum ECP and slL-2R levels were significantly correlated with disease severity before as well as after steroid treatment. Changes of sIL-2R concentrations were strongly related to the changes of ECP levels. In addition, changes of serum sIL-2R and ECP levels in percentage were correlated with clinical improvement. These results indicate that the determination of sIL-2R and ECP serum levels may be useful in monitoring disease activity in atopic dermatitis in childhood, especially in treatment trials.     

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.     

Soluble E-selectin correlates with disease activity in cyclosporin A-treated patients with atopic dermatitis

BACKGROUND: The expression of adhesion molecules on endothelial cells regulates leukocyte migration. The level of soluble adhesion molecules which are shed into the circulation is known to reflect the degree of inflammation, and this level can therefore be used as an indicator of disease activity. The objective of this study was first to investigate the relationship between sE-selectin levels and disease activity parameters (scores of extent, severity, itch, and sleep) in atopic dermatitis (AD) patients, and second to determine the effect of therapy with an immunosuppressive drug (cyclosporin A) on sE-selectin levels. METHODS: Fourteen patients with severe AD and 41 healthy controls were studied. sE-selectin was measured by ELISA both 2 weeks before therapy with cyclosporin A and after 16 weeks of treatment. RESULTS: At baseline, the level of sE-selectin was significantly higher in patients with AD than in healthy control subjects (P<0.0001). After treatment of AD with cyclosporin A, there was a significant reduction of the sE-selectin levels (P<0.0001). In addition, changes in sE-selectin levels significantly correlated with changes in disease activity parameters such as severity (P<0.002) and extent of disease (P<0.049). CONCLUSIONS: Soluble E-selectin is a new serologic marker in AD which reflects disease activity. Therefore, soluble E-selectin may be a useful parameter in the monitoring of this disease.     

Morphological aspects of LFA-1/ICAM-1 and VLA4/VCAM-1 adhesion pathways in human lymph nodes

Monoclonal antibodies specific for the adhesion molecules participating in lymphocyte homing, lymphocyte function associated antigen-1 (LFA-1) and very late antigen 4 (VLA4), and their respective ligands, intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), were used to characterize their expression pattern in human lymph nodes by immunohistochemical and immunoelectron microscopic techniques. The location of LFA-1-positive lymphocytes and selective expression of ICAM-1 on the luminal plasma membrane of high endothelial venule endothelium suggested that the LFA-1/ICAM-1 adhesion pathway participates only in the initial step of the lymphocyte migration process. Lymphocytes passing through endothelium appear not to be influenced by this pathway. VCAM-1 was detected occasionally on the endothelium of high endothelial venules in the hyperplastic lymph nodes in the mesentery, but not in peripheral lymph nodes. VLA4-positive lymphocytes tended to be more frequently observed within high endothelial venules in mesenteric lymph nodes than in peripheral ones. Strong expression of both ligands, ICAM-1 and VCAM-1, was noted on the plasma membrane of follicular dendritic cells, and was especially prominent on their labyrinthine folding, and on the interdigitating cells in the paracortex. Furthermore, both LFA-1-and VLA4-positive lymphocytes localized around these cells. This suggests that LFA-1/ICAM-1 and VLA4/VCAM-1 adhesion pathways play an important role in the lymphocyte recognition of antigen-presenting cells.     

ICAM-1和VCAM-1参与脑胶质瘤侵袭生长

目的探讨脑胶质瘤向周围正常脑组织的侵袭生长与细胞间黏附分子-1(ICAM-1)及血管-细胞黏附分子-1(VCAM-1)的关系。方法共收集44例脑胶质瘤病例,取瘤周组织、肿瘤中心和正常脑组织标本,分别用免疫组化(IHC)、反转录PCR(RT-PCR)和蛋白免疫印迹(Western blot)法检测ICAM-1及VCAM-1在3组标本中的表达量。结果瘤周组织、肿瘤中心组织及正常脑组织比较ICAM-1及VCAM-1表达有显著差异(P0.05);当进行组间两两比较时有显著差异(P0.01),瘤周组织中表达量最高,肿瘤中心组织次之,正常脑组织最少,将标本分为LGGs组和HGGs组后进行比较可得出同样结论。结论 ICAM-1和VCAM-1与脑胶质瘤向周围正常脑组织的侵袭生长有密切关系。     

PPARgamma expression profile and its cytokine driven regulation in atopic dermatitis

BACKGROUND: Recent studies point to the pathophysiological role of the peroxisome proliferators-activated receptor gamma (PPARgamma) in the inflammatory immune response. We have showed that activation of PPARgamma by specific ligands attenuates the allergic immune response via monocytes and lymphocytes. The objective of this study was to analyse the PPARgamma expression and its regulation via inflammatory cytokines. METHODS: We examined the PPARgamma expression in the lesional and nonlesional skin of atopic patients by immunohistochemistry. The expression patterns of PPARgamma mRNA and its isoforms were investigated in peripheral mononuclear blood cells of atopic and nonatopic donors and in cytokine-stimulated populations by quantitative real-time RT-PCR. RESULTS: Our data show an increased PPARgamma expression in lesional skin from atopic dermatitis patients. The analysis of PPARgamma mRNA reveals a significantly up-regulated expression of PPARgamma1 but not of PPARgamma2 in monocytes and CD4(+) T-cells from atopic dermatitis patients. Furthermore, we demonstrate that Th-cytokines, like IL-4, IL-13 and IFNgamma, which regulate the biphasic atopic immune response, directly regulate the expression of PPARgamma1. CONCLUSION: Taken together, these data demonstrate that PPARgamma isoforms are differently expressed and regulated by the local cytokine-milieu. Whether the increased expression of the PPARgamma1 receptor may be beneficial or not for a PPARgamma ligand-based treatment of atopic dermatitis, is currently under investigation.     

Molecular mechanisms involved in intraepithelial lymphocyte migration: A comparative study in skin and tonsil

Intraepithelial lymphocyte migration is a biological process frequently observed in skin and tonsil. Using immuno-histochemistry, we have studied the molecular bases of this process in seven skin biopsies involved by mycosis fungoides (MF) and in 12 tonsils, four involved by B-chronic lymphocytic leukaemia (B-CLL) and eight by lymphoid follicular hyperplasia (LH). In the skin, intraepidermal T-lymphocyte infiltration was associated with narrowing and fragmentation of the basement membrane, as shown by an anti-collagen type IV antibody. Immunostaining of serial sections with an anti-collagenase type IV antibody revealed that collagenase type IV was localized in the upper dermis and Strictly co-distributed with collagen type IV, suggesting that enzymatic digestion played a role in the alterations of the basement membrane. Further migration through the epidermis was mediated by expression on keratinocytes of intercellular adhesion molecule-1 (ICAM-1) and of leukocyte-function associated antigen-1 (LFA-1) on infiltrating lymphocytes. In the tonsil, intraepithelial infiltration was mediated by the expression of vascular cell adhesion molecule-1 (VCAM-1) by epithelial cells and of very late antigen-4 (VLA-4) by infiltrating lymphocytes. Further intraepithelial lymphocyte migration was then established, as already shown in the skin, by ICAM-1/LFA-1 interaction. Lymphocyte recruitment from the systemic circulation was studied using antibodies directed against endothelial leukocyte adhesion molecule-1 (ELAM-1), ICAM-1, and VCAM-1. These adhesion molecules were highly expressed by blood vessels in the upper dermis of MF and the percentage of ELAM-1 +/VCAM-1 + vessels was significantly higher than that observed in tonsils. Our data suggest that distinct molecular mechanisms are used by lymphocytes in intraepithelial migration in the skin and in tonsils.     

The development of atopic dermatitis is independent of Immunoglobulin E up-regulation in the K14-IL-4 SKH1 transgenic mouse model

Background We have successfully generated an IgE‐associated (extrinsic/allergic) mouse model of atopic dermatitis in K14‐IL‐4‐Tg/CByB6 mice. The newly described subset of non‐IgE‐associated (intrinsic/non‐allergic) atopic dermatitis in human patients raises the question on the role of IgE in the pathogenesis. Objective The aim of this study was to develop a non‐IgE‐associated atopic dermatitis model in K14‐IL‐4‐Tg/SKH1 mice. Methods K14‐IL‐4‐Tg/CByB6 mice were crossed with SKH1 mice to produce K14‐IL‐4‐Tg/SKH1 mice. Phenotypes of clinical and histological, cytokine expression in the skin lesions, and total serum IgE in K14‐IL‐4‐Tg/CByB6 and K14‐IL‐4‐Tg/SKH1 mice were compared. The CD40 and CD40L on T and B cells were also studied to differentiate their roles in IgE production. Results K14‐IL‐4‐Tg/SKH1mice had a normal total serum IgE level and manifested a chronic inflammatory skin phenotype identical to that of K14‐IL‐4‐Tg/CByB6 IgE‐mediated mice in clinical morphology, histology, infiltration of mononuclear cells/eosinophils/mast cells, mast cell degranulation, and up‐regulation of chronic lesional cytokine mRNA expression of IL‐1β, IL‐3, IL‐4, IL‐6, IL‐10, IL‐12, IL‐13, IFN‐γ, TNF‐α, and TNF‐β. We also found that the inability of CD4⁺ T cells of the K14‐IL‐4‐Tg/SKH1mice to up‐regulate CD40L expression upon stimulation might account for their inability to up‐regulate the IgE level. B cell abnormality was ruled out as CD19⁺ B cells of K14‐IL‐4‐Tg/SKH1 mice synthesized the same amount of IgE in vitro compared with K14‐IL‐4‐Tg/CByB6 mice in the presence of IL‐4 and soluble CD40L. Our studies further suggested that the defect of early growth response‐1 in T cells might be responsible for the impaired CD40L up‐regulation in K14‐IL‐4‐Tg/SKH1 mice. Conclusion K14‐IL‐4‐Tg/SKH1 mice developed skin inflammation that resembled human intrinsic atopic dermatitis. Therefore, this model may be suitable to study the pathogenesis of intrinsic atopic dermatitis.     

Proteasome inhibitors block VCAM-1 and ICAM-1 gene expression in endothelial cells without affecting nuclear translocation of nuclear factor-ϰB

Endothelial cells play a major role in recruiting leukocytes to sites of inflammation. This is accomplished, at least in part, by up-regulation of cell surface adhesion molecules, including VCAM-1 and ICAM-1, in response to cytokines. In this report, we investigated the role of the proteasome complex in mediating the interleukin (IL)-1β induction of VCAM-1 and ICAM-1 gene expression in human endothelial cells. We present evidence that a proteasome inhibitor, n-acetyl-leucinyl-leucinyl-norleucinal (norLEU), as well as specific protease inhibitors, n-tosyl-Lys-chloromethylketone and n-tosyl-Phe-chloromethylketone, blocked IL-1β induction of VCAM-1 and ICAM-1 promoter-driven reporter gene expression in stably transfected endothelial cells. These inhibitors also blocked cytokine induced cell surface expression of VCAM-1 and ICAM-1 by human umbilical vein endothelial cells. As expected, the protease inhibitors blocked the activation of nuclear factor (NF)-?B in response to IL-1β stimulation. In contrast, norLEU did not prevent IL-1β-induced nuclear translocation of NF-?B. The effects of norLEU were specific because it did not inhibit the IL-1β induction of plasminogen activator inhibitor type 1 gene expression. This study demonstrates that inhibition of the proteolytic activity of the proteasome blocks IL-1β induction of VCAM-1 and ICAM-1 gene expression in human endothelial cells.     

脑血管内皮细胞ICAM-1的表达对T淋巴细胞与内皮细胞粘附的影响

为研究血脑屏障内皮细胞ICAM 1的表达对T淋巴细胞与内皮细胞粘附的影响 ,本实验采用液氮冷冻Wistar大鼠脑组织制成血管源性脑水肿模型 ,将脑组织制成冰冻切片 ,与大鼠T淋巴细胞悬液共温后 ,常规HE染色和显微镜观察 ,求出T淋巴细胞与脑血管壁的特异性粘附率。结果发现事先未滴加抗ICAM 1单抗组 ,T淋巴细胞的特异性粘附率 (均值 :6 2 % )较高 ,而事先滴加抗ICAM 1单抗组 ,T淋巴细胞的特异性粘附率 (均值 :30 % )明显下降 (P <0 0 0 0 1) ,但并未被完全抑制 ,说明ICAM 1是介导T淋巴细胞粘附的重要的粘附分子之一。     

Up-regulation of intercellular adhesion molecule-1 (ICAM-1), endothelial leucocyte adhesion molecule-1 (ELAM-1) and class II MHC molecules on pulmonary artery endothelial cells by antibodies against U1-ribonucleoprotein

In order to elucidate the pathogenic role(s) of autoantibodies in connective tissue disease (CTD), we examined whether autoantibodies against U1-ribonucleoprotein (RNP) and double-stranded (ds) DNA can up-regulate ICAM-1, ELAM-1 and class I and II MHC molecule expression on pulmonary artery endothelial cells (HPAEC). ICAM-1, ELAM-1 and class II MHC molecule expression on HPAEC cultured in the presence of anti-U1-RNP-containing and anti-dsDNA-containing IgG from CTD patients was up-regulated significantly in comparison with that on HPAEC cultured with IgG from normal healthy volunteers. Affinity chromatographic enrichment and depletion of the anti-U1-RNP antibody content of anti-U1-RNP-containing IgG confirmed that the anti-U1-RNP antibody did up-regulate ICAM-1, ELAM-1 and class II MHC molecule expression. The finding that an IgG F(ab')2-purified anti-U1-RNP antibody also up-regulated expression of these molecules may indicate that mechanisms other than Fc receptor-mediated stimulation are involved. These in vitro findings suggest that autoantibodies against U1-RNP and dsDNA play important roles in the immunopathological processes leading to the proliferative pulmonary arterial vasculopathy observed in CTD patients with pulmonary hypertension by up-regulating adhesion and class II MHC molecule expression on endothelial cells.     

IL-31在特应性皮炎中的表达及与瘙痒关系的机制研究

观察内、外源性特应性皮炎患儿白介素31(IL-31)表达并探讨IL-31与特应性皮炎(AD)瘙痒、皮损严重度的关系和可能的作用机制。应用相对定量实时PCR方法检测28例AD患儿和22例正常儿童外周血单个核白细胞(PBMC)IL-31 mR-NA表达水平。对AD患儿进行搔抓、失眠、皮损面积、皮损严重度评分和相关实验室检查。同时免疫组化法检测AD皮损和正常人皮肤IL-31功能受体A(IL-31RA)表达与分布。结果:AD患儿PBMC IL-31表达高于正常对照(P<0.05)。外源性AD较内源性AD PBMC表达IL-31 mRNA略有升高,但无统计学意义。AD患儿IL-31表达与疾病严重程度SCORAD评分呈正相关(r=0.495,P<0.05),同时,IL-31与瘙痒评分也呈正相关关系(r=0.584,P<0.05)。IL-31RA表达在皮肤表皮细胞胞浆内,AD皮损IL-31RA表达显著高于正常人皮肤(P<0.001),并且在触觉小体、环层小体被囊以及神经纤维束有较强表达。IL-31可能不是内、外源性AD免疫学差异的主要因素,但IL-31与AD瘙痒发生密切相关,其表达量可以反映病情严重程度。     

Adhesion molecules from the LFA-1/ICAM-1, 3 and VLA-4/VCAM-1 pathways on T lymphocytes and vascular endothelium in Graves' and Hashimoto's thyroid glands

Lymphocytic infiltration of the thyroid gland in autoimmune thyroid disorders requires, as a first step, their attachment to endothelial cells (EC) and, subsequently, their interaction with thyrocytes and extracellular matrix proteins. A number of different ligand molecules have been identified to mediate the interaction between EC and leukocyte subpopulations. In this study, we examined by flow cytometry and immunohistochemical techniques, the expression of integrin receptors and their counter-receptors by infiltrating lymphocytes and vascular endothelium in thyroid glands from patients with Graves' disease (GD) and Hashimoto's thyroiditis (HT). A high proportion of GD intrathyroidal T lymphocytes expressed the CD69 and gp95/85 (Ea2) activation antigens as well as an increased number of LFA-α_L, VLA-α1, -α4, -α5, and -β1 integrin receptors, as compared with peripheral blood T lymphocytes from the same patients. The expression of intercellular adhesion molecule (ICAM)-1 was increased in EC from GD and HT thyroids. In addition, an up-regulated de novo expression of vascular cell adhesion molecule (VCAM)-1 was found in EC in GD and HT thyroids, with no reactivity in control thyroids. Dendritic cells in thyroid lymphoid follicles were also positive for ICAM-1 and VCAM-1. In addition, most of intrathyroidal mononuclear cells expressed the ICAM-3 adhesion molecule. This enhanced expression of ICAM-1 and VCAM-1 by thyroid EC in GD and HT may reflect their ability to regulate leukocyte trafficking and activation by means of the expression of specific ligand molecules. Our data suggest that both the LFA-1/ICAM-1, ICAM-3 and VLA-4/VCAM-1 pathways could play a relevant role in localizing and perpetuating the autoimmune response in the thyroid gland in autoimmune thyroid disorders.     

Modulation of intercellular adhesion molecule 1 (ICAM-1) expression on the human mast-cell line (HMC)-1 by inflammatory mediators

The effect of inflammatory mediators on the expression of several surface adhesion molecules on the human mast-cell line (HMC)-1 was studied. By flow cytometry, it could be shown that among several surface adhesion molecules (ICAM-UCDS4, VLA-4/CD49d, Mac-UCD11b, LFA-1/CD11a, LFA-2/CD2, LFA-3/CDS8, VCAM-1), only the constitutively expressed immunoglobulin family member intercellular adhesion molecule-1 (ICAM-1) is modulated by proinflammatory cytokines on HMC-1 mast cells. Stimulation with tumor necrosis factor-a (TNF-α) and interferon-γ (IFN-γ) resulted, in addition to interleukin-(lL-)4, in selective upregulation of ICAM-1 expression. Costimulation of either IL-4 or IFN-γ with TNF-α further increased the ICAM-1 expression as compared to the stimuli alone. In contrast, stem-cell factor (SCF), granulocyte/macrophage colonystimulating factor (GM-CSF), IL-10, IL-8, monocyte chemotactic and activating factor (MCAF), and the complement split product C5a failed to modulate the expression of any adhesion molecule examined. The levels of cytoplasmic free calcium in HMC-1 mast cells were not altered by cross-linking surface ICAM-1, suggesting linkage of other intracellular signaling pathways. This cytokine-induced upregulation of ICAM-1 expression might reveal a putative regulatory mechanism of mast-cell interaction with effector cells bearing the counterparts of ICAM-1 (CD54), the molecules Mac-1 (CD11b/CD18) and leukosialin (CD43), and the principal ligand LFA-1 (CD11a/CD18).     

Leukotriene B4 in atopic dermatitis: increased skin levels and altered sensitivity of peripheral blood T-cells

Employing a radioimmunoassay, de-proteinated suction blister fluid from 12 patients with active atopic dermatitis appeared to contain higher levels of the pro-inflammatory and immunomodulatory mediator leukotriene B4 (LTB4) than suction blister fluid from 12 non-atopic individuals. Indirect support for the identity of the mediator was obtained by HPLC of pooled samples. Nylon wool enriched T cells from six patients with atopic dermatitis and six non-atopic people preincubated with LTB4 (10(-10) M - 10(-8) M) expressed no statistically significant suppression in co-culture with mitogen stimulated autologous mononuclear cells, and there was no difference between atopic and non-atopic T cells in this respect. In contrast, LTB4 induced a dose-dependent reduction in the percentage of phenotypic Leu 2a (suppressor) cells leading to an increased helper/suppressor ratio in five atopic patients that was not observed in five non-atopics. Elevated skin levels of LTB4 may initiate or amplify dermal inflammation, and abnormal T cell response to the mediator may account for the increased helper/suppressor ratio characteristic of patients with atopic dermatitis.     

GM-CSF, IL-1 alpha, IL-1 beta, IL-6, IL-8, IL-10, ICAM-1 and VCAM-1 gene expression and cytokine production in human duodenal fibroblasts stimulated with lipopolysaccharide, IL-1 alpha and TNF-alpha.

The role of mucosal fibroblasts in intestinal inflammatory reactions is not known. In this study, we demonstrate that fibroblasts grown from histologically normal human duodenal biopsy tissues expressed mRNA genes for granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-1 alpha, IL-1 beta, IL-6, IL-8, IL-10, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) when stimulated with lipopolysaccharide (LPS) or IL-1 alpha. The increased mRNA expression of GM-CSF, IL-1 alpha, IL-1 beta, IL-6 and IL-8 in response to IL-1 alpha and LPS stimulation was time- and dose-dependent. In contrast, IL-10 was weakly expressed when fibroblasts were stimulated with LPS, IL-1 alpha or tumour necrosis factor-alpha (TNF-alpha), but the expression was enhanced in the presence of cycloheximide combined with optimal concentrations of LPS, IL-1 alpha or TNF-alpha, IL-1 alpha was a more potent stimulator than LPS for GM-CSF, IL-6, IL-8 and IL-10 expression, but not for IL-1 alpha and IL-1 beta. Increased GM-CSF, IL-6 and IL-8 gene expression was associated with the production of cytokine proteins in culture supernatant, but IL-1 alpha and IL-1 beta remained undetectable. Dexamethasone suppressed both gene expression and protein production of GM-CSF, IL-6 and IL-8 when fibroblasts were exposed to IL-1 alpha. TNF-alpha stimulated the release of GM-CSF, IL-6 and IL-8 and, combined with IL-1 alpha, cytokine production was enhanced synergistically. Finally, both LPS and IL-1 alpha up-regulated ICAM-1 and VCAM-1 gene expression. These findings implicate duodenal fibroblasts in the initiation and/or regulation of intestinal inflammation.     

Adhesion molecules (E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)) in sera from patients with Staphylococcus aureus bacteraemia with or without endocarditis

The aim of this prospective study was to evaluate if patients with endocarditis display a more extensive endothelial activation than those with bacteraemia but without endocarditis. Sixty-five patients with blood culture-verified Staphylococcus aureus bacteraemia were included and serum samples collected on admission were analysed by enzyme immunoassays. Elevated serum concentrations of adhesion molecules were found in most of the patients with S. aureus bacteraemia. Patients with endocarditis (n = 15) showed significantly higher serum E-selectin (median 156 ng/ml) and VCAM-1 (median 1745 ng/ml) concentrations compared with those with S. aureus bacteraemia but without endocarditis (80 ng/ml and 1172 ng/ml, respectively; P = 0.01 and P = 0.003). No significant difference was found between the groups concerning ICAM-1 (median 451 ng/ml versus 522 ng/ml). In addition, serum tumour necrosis factor-alpha (TNF-alpha) concentrations were significantly correlated (P < 0.002) to serum levels of E-selectin, ICAM-1 and VCAM-1.