Effectiveness of papaverine cisternal irrigation for cerebral vasospasm after aneurysmal subarachnoid hemorrhage and measurement of biomarkers

Cisternal irrigation with thrombolytic agents was used to prevent post-SAH vasospasm, but its role remained inconclusive. To verify effectiveness of papaverine (PPV) in preventing vasospasm, we studied relationship between inflammatory biologic markers and vasospasm. This prospective study included 121 patients with clipped anterior circulation aneurysms that had ruptured, and 372 control patients. Patients were divided into three groups according to cisternal irrigation method: simple drain, papaverine group, and urokinase (UK) group. Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were determined in CSF and serum on days 3 and 7 after SAH. The PPV group showed similar incidence of vasospasm with UK group, but lower incidence than the simple drain group. The levels of ICAM-1 and VCAM-1 were significantly higher in the SAH group than in the control group. CSF and serum levels were more elevated on day 7 than day 3, and the degree of elevation were more marked when measured in the CSF than in the serum. However, there was no statistical difference between measured levels of ICAM-1 and VCAM-1, and vasospasm development. PPV cisternal irrigation was similarly effective as UK at preventing vasospasm. Although neither PPV nor UK irrigation could reduce the concentration of adhesion molecules compared with simple drain, we found levels of ICAM-1 and VCAM-1 were specifically elevated in the CSF. Therefore, further research should focus on anti-inflammation as a therapeutic target against cerebral vasospasm and on the CSF as the optimum place where such inflammatory action practically brought about.     

Circulating,soluble adhesion proteins in cerebrospinal fluid and serum of patients with multiple sclerosis: Correlation with clinical activity

Soluble adhesion protein intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and endothelial leukocyte adhesion molecule (E-selectin) were measured in serum and cerebrospinal fluid (CSF) of patients with relapsing-remitting multiple sclerosis (RRMS) in remission and in exacerbation, as well as patients with chronic progressive MS, stable MS, and in patients with other neurological and inflammatory diseases (ONDs). Serum ICAM-1 and E-selectin were significantly elevated in patients with MS over those with ONDs and controls. CSF VCAM-1 and E-selectin were found to be elevated over control and disease control samples. No increase in CSF ICAM-1 was observed. Results were analyzed longitudinally and by MS category. In paired CSF and serum samples from patients in exacerbation, elevated VCAM-1 correlated with increased serum VCAM-1 in 5 of 7 patients. Elevated CSF E-selectin did not correlate with elevations in serum E-selectin.     

Cell surface adhesion molecules and cytokine profiles in primary progressive multiple sclerosis

OBJECTIVE: We evaluated the utility of adhesion molecule (AM) and cytokine/chemokine expressions in blood and cerebrospinal fluid (CSF) as markers of disease activity in primary progressive multiple sclerosis (PPMS). METHODS: The expressions of AMs and the levels of 17 cytokines in patients with PPMS (n = 25) were compared with those in secondary progressive MS (SPMS) (n = 18) and controls (n =11) and correlated with the volumes of focal and atrophic changes on MRI. RESULTS: The expressions of very late activation antigen 4 (VLA-4), lymphocyte function-associated antigen 1 (LFA-1) and intercellular adhesion molecule 1 (ICAM-1) in blood and CSF were higher in PPMS than in controls. Comparison between PPMS and SPMS showed higher levels of ICAM-1 in blood and CSF in PPMS, while the level of the vascular adhesion molecule (VCAM-1) was higher only in blood. There was no difference in the levels of cytokines in serum or CSF between PPMS and SPMS or controls, but evidence suggesting intrathecal synthesis of interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) was found in PPMS. The expressions of CSF VLA-4 in PPMS correlated with the total volume of cerebral lesions and the number of diffuse brain lesions in MRI, while the amount of LFA-1 in CSF correlated with the number of spinal T2 lesions. The level of serum MIP-1beta correlated with the T2 lesion load and EDSS score in PPMS. CONCLUSIONS: The upregulated expressions of AMs in blood and CSF and evidence for intrathecal synthesis of MCP-1 and IL-8 in PPMS indicate the importance of inflammatory changes in the pathogenesis of PPMS.     

Expression of adhesion molecules and monocyte chemoattractant protein-1 (MCP-1) in the spinal cord lesions in HTLV-I-associated myelopathy

Leukocyte adhesion molecules to endothelium plays an important role in the pathogenesis of inflammatory diseases, including HTLV-I-associated myelopathy (HAM)/tropical spastic paraparesis (TSP). To help define the role of adhesion molecules in HAM/TSP, we studied the expression of lymphocyte function-associated antigen-1 (LFA-1), Mac-1, very late antigen-4 (VLA-4), Sialyl Lewis^x (SLex), intercelluar adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), endothelial leukocyte adhesion molecule-1 (ELAM-1) and monocyte chemoattractant protein-1 (MCP-1) in the spinal cord lesions of HAM/TSP. The results indicate that spinal cord lesions of HAM/TSP have greater VCAM-1 expression on endothelium compared with those of controls. Infiltrating mononuclear cells, especially perivascular lesions, expressed VLA-4. Although the expression of ICAM-1 in the spinal cords was not distinctive between HAM/TSP and controls, infiltrating mononulcear cells in the spinal cords of HAM/TSP strongly expressed LFA-1 and Mac-1. ELAM-1 was expressed on endothelium in the inactive-chronic lesions from three of five HAM/TSP, but was not detectable in the spinal cords of controls. SLex reaction was detectable on occasional perivascular cells in the spinal cord of HAM/TSP, but not in those of controls. MCP-1 was detectable on perivascular infiltrating cells and vascular endothelium in active-chronic lesions. This study suggests that VLA-4/VCAM-1 interaction may play an important role for lymphocyte migration into the central nervous system (CNS), and MCP-1 may also be involved in inflammatory cell recruitment to the CNS in HAM/TSP. Received: 4 September 1995 / Revised, accepted: 23 October 1995     

Serum and cerebrospinal fluid levels of soluble adhesion molecules in multiple sclerosis: predominant intrathecal release of vascular cell adhesion molecule-1

Activated cerebral vascular endothelial cells express leukocyte, vascular cell, and intracellular adhesion molecules (E-selectin, VCAM-1 and ICAM-1) which facilitate leukocyte adhesion to endothelium and migration into inflammatory lesions. Paired serum and cerebrospinal fluid (CSF) levels of soluble (s) E-selectin, sVCAM-1 and sICAM-1 were determined by ELISA in patients with clinically definite MS in relapse, and patients with other inflammatory (IND) and non-inflammatory neurological disease (NIND). CSF levels of sVCAM-1 and sICAM-1 were significantly increased in MS patients compared to IND and NIND patients. Elevation of CSF sVCAM-1 in MS patients was the most marked finding (P = 0.0001) and an increased sVCAM-1 index indicated that this was due to intrathecal release of sVCAM-1. There were no differences in serum and CSF sE-selectin levels between the study groups. Measurement of the sVCAM-1 index may provide a marker of disease activity in patients with clinically definite MS.     

Differential effects of moderate or heavy alcohol consumption on circulating adhesion molecule levels

Epidemiological studies suggest that moderate but not heavy alcohol consumption provides protection against coronary heart disease. We assessed the relationship between alcohol consumption and serum levels of adhesion molecules involved in the pathogenesis of early atherosclerosis. One-hundred apparently healthy men with similar cardiovascular risk factors were divided into four groups according to ethanol intake. Moderate drinkers (20-40 g/day) showed lower serum intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) levels than abstainers (p < 0.05; both), as well as lower serum ICAM-1, VCAM-1 and E-selectin levels than heavy drinkers (p = 0.01; all). The latter also showed higher serum ICAM-1 and E-selectin levels than abstainers (p < 0.001; both). We conclude that moderate drinkers show a significant reduction of soluble endothelial adhesion molecule levels compared to abstainers and heavy drinkers, that may contribute to the protective effect of moderate alcohol consumption against atherosclerosis.     

细胞间粘附分子-1在蛛网膜下腔出血后痉挛血管内的表达

目的：研究细胞间粘附分子－1（ICAM－1）在蛛网膜下腔出血（SAH）后脑血管壁内的表达变化规律及其与脑血管痉挛（CVS）的关系。方法：应用免疫组织化学及逆转录－聚合酶链式反应（RT－PCR）等方法，检测大鼠2次注血SAH模型基底动脉壁内ICAM－1在蛋白质和mRNA水平上的表达。结果：在大鼠脑池内注血后第3d，基底动脉血管腔狭窄已非常明显，第5d达到高峰。注血后第1d,ICAM-1表达开始上调，主要在内膜及内膜下，第3dg表达明显增强并持续到第5d。ICAM－1在蛋白和mRNA水平上表达基本一致，且在时程上的变化与CVS的程度密切相关。结论：由ICAM－1介导的血管壁炎症反应可能在CVS发生和发展过程中起重要作用。     

Temporal variations of adhesion molecules and matrix metalloproteinases in the course of MS

Thirty patients with clinically isolated syndromes (CIS) were evaluated at the onset of neurological symptoms and when they developed clinically definite MS (CDMS). Surface expression of LFA-1, VLA-4 and intercellular adhesion molecule-1 (ICAM-1) on PBMC and CSF cells was evaluated using flow cytometry. Serum and CSF concentrations of soluble vascular cell adhesion molecules-1 (VCAM-1), ICAM-1 and E-Selectin, as well as MMP-9 and MMP-2 serum concentrations were assayed using ELISA. Surface expression of LFA-1 and VLA-4 molecules on peripheral blood and CSF T cells and monocytes from CIS and CDMS was significantly increased compared with control subjects. Moreover, LFA-1 and VLA-4 expression was significantly higher in patients who developed CDMS compared with those with CIS. Similar changes were observed in the serum levels of MMP-9. Furthermore, patients with CIS and CDMS had significantly higher levels of CSF sVCAM and s-E-Selectin than control subjects. These data suggest that VLA-4, LFA-1 and MMP-9 play a leading role in the evolution of inflammatory demyelinating lesions in patients with CIS who develop CDMS.     

Adhesion molecule expression and regulation on cells of the central nervous system.

Cellular adhesion molecules were initially defined as cell surface structures mediating cell-cell and cell-extracellular matrix (ECM) interactions. Adhesion molecules involved in immune responses have been classified into three families according to their structure: selectins, immunoglobulin (Ig) superfamily, and integrins. It has been well documented that adhesion molecules of these family members (E-selectin, ICAM-1, and VCAM-1) are expressed on brain microvessel endothelial cells in active lesions of multiple sclerosis (MS) brain. In addition, accumulating data show that glial cells can express some of these adhesion molecules upon activation: astrocytes can express ICAM-1, VCAM-1, and E-selectin, and microglia express ICAM-1 and VCAM-1. In vitro studies show that these adhesion molecules are actively regulated by several cytokines which have relevance to MS or experimental autoimmune encephalomyelitis (EAE). In addition, soluble forms of adhesion molecules have been found in the serum and cerebrospinal fluid (CSF) of MS patients, and may be useful diagnostically. Experimental therapy of EAE using antibodies against several adhesion molecules clearly shows that adhesion molecules are critical for the pathogenesis of EAE. Thus far, the function of adhesion molecule expression on brain endothelial and glial cells has not been clearly elucidated. Studies on the possible role of adhesion molecules on brain endothelial and glial cells will be helpful in understanding their involvement in immune responses in the central nervous system (CNS).     

Inflammatory molecule expression in cerebral arteriovenous malformations.

Inflammatory proteins may play a role in the pathophysiology of cerebral arteriovenous malformations and their response to radiosurgery. The aim of this study was to compare the expression of inflammatory molecules in arteriovenous malformations (AVMs) with that in normal cerebral vessels. Fresh-frozen surgical specimens from 15 AVMs and three control specimens were studied. The expression of P- and E-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), platelet-endothelial cell adhesion molecule (PECAM-1) and von Willebrand factor were examined using immunohistochemistry. AVMs had significant upregulation of E-selectin. VCAM-1 and ICAM-1 upregulation was also observed in AVMs. Pre-operative embolization was associated with increased expression of E-selectin and VCAM-1. This study has provided further evidence that the endothelium of AVMs has different molecular properties than the endothelium of normal cerebral vasculature. Inflammatory molecules may be biologically relevant in the response of vascular malformations to radiosurgery and embolization.     

Acupuncture for cerebral ischemia/reperfusion injury Does it reduce the inflammatory reaction?

BACKGROUND:Nuclear factor-κB (NF-κB), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) in brain tissue can participate in inflammatory reactions after cerebral ischemia.Acupuncture treatment for acute cerebral ischemia produces abnormal protein expression.OBJECTIVE:To investigate the effects of acupuncture on NF-κB, ICAM-1, and VCAM-1 mRNA and protein expression in the brain tissue of rats with cerebral ischemia/reperfusion injury.DESIGN, TIME AND SETTING:Randomized...     

Neuropathological evidence for ischemia in the white matter of the dorsolateral prefrontal cortex in late-life depression

BACKGROUND: Signal hyperintensities on magnetic resonance imaging in late-life depression are associated with treatment resistance and poor outcome. These lesions are probably vascular in origin and proposed sites for vascular damage include the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC). METHODS: We therefore examined white matter in these areas for microvascular disease and evidence of ischemia using intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1). We obtained postmortem tissue from elderly depressed (n = 20) and control (n = 20) subjects and blindly rated microvascular disease and ICAM-1 and VCAM-1 amount using quantitative image analysis in sections of the DLPFC, ACC and occipital cortex (OC; control area). RESULTS: We found a significant increase in ICAM-1 in the deep white matter of the DLPFC in the depressed group (p = 0.01) and a trend towards an increase for VCAM-1 (p = 0.10). In the gyral white matter there was a trend towards significance for both molecules (p = 0.07 and 0.10). No differences were found in the ACC or OC or for microvascular disease in any area. CONCLUSIONS: These findings are consistent with white matter ischemia in the DLPFC and lend support to the 'vascular depression' hypothesis. They implicate the DLPFC as an important site in the pathogenesis of late-life depression and have major implications for the understanding and management of late-life depression and raise the possibility of novel treatments being introduced in the future.     

LFA-1 and VLA-4 involved in human high proliferative potential-endothelial progenitor cells homing to ischemic tissue

Cumulative evidences have revealed that endothelial progenitor cell (EPC) transplantation can promote the neovascularization in ischemic tissue, but the mechanism of EPCs homing to the site of ischemia is poorly understood. In this study, to investigate the mechanism of human umbilical cord blood-derived high proliferative potential-endothelial progenitor cells (HPP-EPCs) homing to ischemic tissue we evaluated the expression of lymphocyte function-associated antigen-1 (LFA-1, or CD11a/CD18) and very late antigen-4 (VLA-4, or CD49d/CD29) in EPCs and the changes of expression level of their ligands, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), in ischemic tissue and performed the adhesion and migration assays to analyze the interaction between the receptors and ligands. Furthermore, we studied the roles of LFA-1 and VLA-4 in EPC homing in an ischemic model of mice. The results show that LFA-1 andVLA-4 were expressed in HPPEPCs and ICAM-1 and VCAM-1 were expressed in vessel endothelium in ischemic tissues. The pre-incubation of HPP-EPCs with neutralizing antibodies against CD11a or CD49d reduced adhesion and migration of HPP-EPCs in vitro and reduced recovery of hind-limb blood flow, capillary density and incorporation of HPP-EPC into ischemic tissues in vivo. Furthermore, the pre-incubation of HPP-EPCs with the combination of CD11a and CD49d antibodies led to synergistically negative effects on adhesion and transmigration of HPP-EPCs in vitro, and on the homing of HPP-EPCs to ischemic tissue and on neovascularization capacity in vivo. These results indicate that LFA-1 andVLA-4 are involved in HPP-EPC homing to ischemic tissues.     

Vascular cell adhesion molecule-1 modulation by tumor necrosis factor in experimental allergic encephalomyelitis

Anti-tumor necrosis factor (TNF) antibodies inhibit passively transferred experimental allergic encephalomyelitis (EAE) in SJL mice. The possibility that this occurs through interference in TNF's upregulation of endothelial cell adhesion molecules was investigated. Expression of both vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) on spinal cord vessels increased during EAE. The upregulation of VCAM-1 was markedly reduced or prevented by anti-TNF treatment. Leukocytic infiltration was 15-fold lower in anti-TNF-treated than diseased animals. Spinal cord endothelial expression of VCAM-1, though not ICAM-1 or fibronectin, positively correlated with the extent of T cell, B cell or monocyte infiltration in each animal.     

sPECAM-1 in serum and CSF of acute ischaemic stroke patients

OBJECTIVES: As platelet endothelial cell adhesion molecule-1 (PECAM-1) is one of key mediators of transendothelial migration of leucocytes during inflammation, and inflammatory reaction is observed in cerebral ischaemia, we decided to determine the levels of soluble PECAM-1 (sPECAM-1) in serum and cerebrospinal fluid (CSF) of patients with acute stroke. MATERIAL AND METHODS: Twenty-three patients with first-ever in a lifetime completed ischaemic stroke have been studied. CSF and blood samples were obtained within 24 h of the onset of stroke and the levels of sPECAM-1 in serum and CSF were quantified by ELISA. RESULTS: Stroke patients displayed statistically significant higher levels of sPECAM-1 in sera and CSF in comparison with control group. The levels were significantly higher in serum than in CSF, correlated between each other, and CSF sPECAM-1 fraction was blood-derived. CONCLUSION: Our results indirectly suggest that PECAM-1 may play a role in the pathophysiological events during early phase of ischaemic stroke.     

Anti-VCAM-1 antibodies did not protect against ischemic damage either in rats or in mice.

Cerebral ischemia triggers an inflammatory process involving the infiltration of leukocytes to the parenchyma. Circulating leukocytes adhere to the vascular wall through adhesion molecules. Here we quantified the in vivo expression of vascular cell adhesion molecule-1 (VCAM-1) in the brain, heart and lungs from 6 to 48 h after transient middle cerebral artery (MCA) occlusion in rats, by intravenous injection of a tracer radiolabelled anti-VCAM-1 antibody. The vascular localization of VCAM-1 was verified by immunohistochemistry after in vivo injection of the antibody. Vascular cell adhesion molecule-1 was strongly induced (4-fold at 24 h) in the microvasculature of the ischemic area, and, to a lesser extent, in the contralateral hemisphere and in a remote organ, the heart, but not in the lungs, indicating that the inflammatory process propagates beyond the injured brain. We injected intravenously either blocking doses of anti-VCAM-1 antibodies or control antibodies after MCA occlusion in rats and mice. We evaluated the neurological score in rats, and infarct volume at 2 days in rats and at 4 days in mice. Anti-VCAM-1 did not protect against ischemic damage either in rats or in mice. Vascular cell adhesion molecule-1 blockade significantly decreased the number of ED1 (labeling monocytes /macrophages/reactive microglia)-positive cells in the ischemic rat brain. However, it did not reduce the numbers of infiltrating neutrophils and lymphocytes, and total leukocytes (CD45 positive), which showed a trend to increase. The results show vascular upregulation of VCAM-1 after transient focal ischemia, but no benefits of blocking VCAM-1, suggesting that this is not a therapeutical strategy for stroke treatment.     

HIV-1 Tat protein upregulates inflammatory mediators and induces monocyte invasion into the brain

Impaired inflammatory functions may be critical factors in the mechanisms by which HIV-1 enters the CNS. Evidence indicates that a viral gene product, the protein Tat, can markedly contribute to these effects. In the present study we tested the hypothesis that Tat can upregulate the expression of inflammatory cytokines and adhesion molecules and facilitate the entry of monocytes into the brain. Expression of inflammatory mediators such as monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-alpha), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) was assessed in C57BL/6 mice injected with Tat(1-72) into the right hippocampus. In the Tat(1-72)-injected groups, mRNA and protein levels of MCP-1, TNF-alpha, VCAM-1, and ICAM-1 were markedly elevated compared to those in control animals. The most pronounced changes were observed in and around the injected hippocampus. Double-labeling immunohistochemistry demonstrated that inflammatory proteins were primarily expressed in activated microglial cells and perivascular cells. In addition, astrocytes and endothelial cells were susceptible to Tat(1-72)-induced inflammatory responses. These changes were associated with a substantial infiltration of monocytes into the brain. These data demonstrate that intracerebral administration of Tat can induce profound proinflammatory effects in the brain, leading to monocyte infiltration.     

Intercellular adhesion molecule-1-deficient mice are less susceptible to cerebral ischemia-reperfusion lnjury

Neutrophil emigration is mediated by adhesion proteins that are highly expressed on the endothelial surface during inflammatory processes in the brain. Intercellular adhesion molecule-1 (ICAM-1) is an inducible adhesion molecule that binds to leukocyte integrins and facilitates neutrophil adhesion and transendothelial migration. To study the role of ICAM-1 during ischemia and reperfusion in the brain, we analyzed the effect of transient focal cerebral ischemia in ICAM-1-deficient mice generated by gene targeting in embryonic stem cells. Transient focal ischemia was induced by occluding the left middle cerebral artery for 3 hours followed by a 21- or 45-hour reperfusion period. When compared with their wild-type littermates, ICAM-1-deficient mice were less susceptible to cerebral injury as demonstrated by a 5.6- or 7.8-fold reduction in infarction volume, respectively. These data support the premise that neutrophil adhesion in ischemic areas may be deleterious and that ICAM-1 deficiency reduces neurological damage after transient focal cerebral ischemia.     

The adhesion molecule and cytokine profile of multiple sclerosis lesions

The expression of the adhesion molecules, vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), and their respective receptors on leukocytes, very late activation antigen-4 (VLA-4) and lymphocyte function–associated antigen-1 (LFA-1), together with a selection of proinflammatory and immunomodulatory cytokines (interleukin [IL]-1, IL-2, IL-4, IL-10, tumor necrosis factor-α [TNF-α], transforming growth factor-β [TGF-β], and interferon-γ [IFN-γ]) was examined by immunocytochemistry in multiple sclerosis (MS) lesions of different ages and compared with central nervous system (CNS) tissue from other neurological diseases, both inflammatory and noninflammatory, and normal CNS tissue. These molecules play key roles in lymphocytic infiltration and interactions during tissue inflammation and are in large part normally not expressed by CNS cells. High levels of expression of all the molecules tested were found in MS, particularly in chronic active lesions. Positivity for all molecules was also seen in other neurological diseases, even in noninflammatory conditions. There was some suggestion that the VCAM-1/VLA-4 adhesion pathway was expressed at higher levels in chronic MS lesions, while ICAM-1/LFA-1 was used more uniformly in lesions of all ages. Of the cytokines examined, there was increased expression of TNF-α and IL-4 in MS; this was found to be statistically significant when compared with noninflammatory neurological diseases. The expression of most adhesion molecules and some cytokines was negligible in normal CNS tissue although low-level reactivity for ICAM-1 TGF-β, IL-4, TNF-α, and IL-10 was detected, perhaps indicative of immunoregulatory mechanisms. Microglial cells and astrocytes were the major CNS cell types expressing cytokines. The results indicate a potential in the CNS for widespread induced expression of molecules involved in the inflammatory cascade. No adhesion or cytokine molecule or pattern of expression unusual for MS was apparent.     

Adhesion molecule expression in experimental myositis

Experimental allergic myositis (EAM) in Lewis rats, induced with partially purified myosin, is regarded as a model of human polymyositis. To clarify the role of adhesion molecules in the pathogenesis of EAM in Lewis rats, we investigated intramysial expressions of the intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1, and the serum level of soluble ICAM-1 in EAM rats. All the EAM rat muscles had scattered inflammatory foci, as well as cell infiltration and necrosis, by week 4 after the initial immunization (i.e., day 0 after the last immunization). As compared with the control muscles, ICAM-1 and VCAM-1 were strongly expressed immunohistochemically in the endothelium of vessels in the endomysium and perimysium, and to lesser extents in the inflammatory infiltrates and on the sarcolemma of nonnecrotic muscle fibers adjacent to the inflammatory infiltrates or invaded muscle fibers. ICAM-1 in the muscle extracts and sera from EAM rats increased on each test day, as compared with extracts from the normal controls. The values peaked on day 0 after the last immunization, then gradually decreased with time. ICAM-1 elevations in the muscle extracts were correlated with the percent of sections that had inflammatory lesions (P = 0.032) and the histological scores (P = 0.005) on day 0, whereas there was no significance on days 3 and 7. These findings suggest that the adhesion molecules ICAM-1 and VCAM-1 increase in the early stage of EAM, and function in the initiation of the inflammatory process of myositis.