The associations between iL-18 serum levels and the prevalence of metabolic syndrome in Polish men over the age of 40 according to other selected inflammatory indices and androgens: comparison of NCEP with IDF criteria.

BACKGROUND: The frequency of MS increases with age and augments the cardiovascular risk. The criteria for distinguishing MS constantly evolve. The aim of the study was to estimate the reciprocal links between low-grade inflammation, selected serum androgens and prevalence of MS, according to NCEP and IDF criteria, in Polish men over the age of 40. MATERIALS AND METHODS: A sample of 160 men was randomly selected from men at the age of 40, 50, 60 and 70, residing in the rural south-western region of Poland. IL-18 and CRP, transferrin, α (1)-antichymotrypsin, dehydroepiandrosterone and its sulfate as well as free-testosterone levels were evaluated. RESULTS: The prevalence of MS was 37.5% using NCEP criteria and 46.25% employing IDF indices. Patients with MS diagnosed according to criteria proposed by NCEP and IDF exhibit a similar hormonal and immunological profile. Age was positively correlated with CRP (r=0.231; p<0.0005), and α (1)-ACT (r=0.191 p<0.05) and negatively with transferrin (r=-0.27; p<0.001), but not with IL-18 plasma levels. Both adrenal androgens were negatively correlated with age: DHEA r=-0.489; p<0.001 and DHEAS: r=-0.553; p<0.001 respectively, in contrast to free-testosterone. People suffering from MS have shown a significantly higher level of IL-18 and CRP. The number of MS components identified (according to NCEP) is positively correlated only with IL-18 serum levels (r=0.226; p=0.043). CONCLUSIONS: Inflammatory parameters were better than a deficit of androgens in identifying men suffering from MS. However, the best correlation with the number of MS components was revealed by IL-18 plasma levels.

PECAM-1, a key player in neuroinflammation.

Platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31) is a 130-kDa protein, which plays a significant role in the adhesion cascade. It is therefore involved in leucocyte endothelium interaction and in leucocyte transendothelial migration during inflammation. As neuroinflammation and subsequent blood brain barrier disruption are integral processes in many neurological disorders, PECAM-1 and its soluble form (sPECAM-1) have been investigated in a number of conditions, rising hopes as a potential marker of disease activity, a possible target in treatment and a prognostic factor. It has been shown that serum and CSF levels of PECAM-1 and sPECAM-1 are increased in patients in active stages of multiple sclerosis. Similarly, they rise in individuals after ischaemic stroke. PECAM-1 has also been shown to be involved in the pathogenesis of Abeta-related cerebral vascular disorders, such as Alzheimer disease. It participates in the pathomechanism of paraneoplastic neurological disorders and in neuroinflammation in NeuroAIDS. A number of experiments on animal models were carried out in order to investigate PECAM-1 role in the above-mentioned conditions and more, including brain trauma and nerve root injury. In this review most recent investigations on PECAM-1 biology and its role in neuroinflammation have been described and discussed from a multidisciplinary point of view.

The level of chemokine CXCL5 in the cerebrospinal fluid is increased during the first 24 hours of ischaemic stroke and correlates with the size of early brain damage.

Inflammation is an important feature of the pathophysiological response to ischaemic stroke. The ischaemic brain-invading leukocytes, neutrophils in particular, contribute to the exacerbation of tissue injury in stroke. Chemokines are a growing family of proteins performing chemotactic activity on selective leukocyte subpopulations. Chemokines are broadly divided into two major subfamilies on the basis of the arrangement of the two N-terminal cysteine residues, CXC and CC, depending on whether the first two cysteine residues have an amino acid between them (CXC) or are adjacent (CC). CXC chemokines possessing, close to the N terminus, the amino acid sequence glutamic acid-leucine-arginine (ELR motif) specifically act on neutrophils. CXCL5 is one of the ELR-expressing CXC chemokines and is a potent neutrophil attractant and activator. The objective of the study was to detect CXCL5 levels in the cerebrospinal fluid (CSF) and sera of stroke patients and to investigate the relation between these levels and the volume of brain computed tomography (CT) hypodense areas representing early ischaemic lesions. A total of 23 ischaemic stroke patients were studied. CSF and blood sampling and brain CT were performed within the first 24 hours of stroke. The control group consisted of 15 patients with tension headache. CXCL5 levels were determined by the ELISA method. CSF CXCL5 levels in stroke patients were significantly higher in comparison with the control group (38.2 +/- 18.4 pg/ml vs. 18.7 +/- 8.2 pg/ml; p < 0.001). No significant differences in serum CXCL5 levels were found between the stroke patients and the control group. CSF CXCL5 levels correlated positively with the volume of early brain CT hypodense areas (p < 0.0001). The results suggest that CXCL5 may play a role in the inflammatory reaction during the early phase of ischaemic stroke.

Interleukin-18 in acute ischaemic stroke patients.

As proinflammatory cytokines released during ischaemia are detrimental to the brain, the study aimed to evaluate serum interleukin-18 (IL-18) levels in stroke patients and to investigate the relation between these and epidemiological and clinical data. The study comprised 23 ischaemic stroke patients and 15 controls. Blood sampling for IL-18 determination and for chemistry, and brain CT were performed within 24 h of stroke, while neurological stroke severity and functional disability were estimated, respectively, with the Scandinavian stroke scale (SSS) and Barthel index (BI) within the same interval and two weeks later. There were higher serum IL-18 levels in stroke patients. These correlated with erythrocyte sedimentation rate (ESR), brain CT hypodense area volumes, and SSS and BI scores calculated at both studied times. Moreover, IL-18 levels were higher in patients with non-lacunar stroke subtype than in those with lacunar strokes. The results suggest that IL-18 is involved in stroke-induced inflammation and that initial serum IL-18 levels may be predictive of stroke outcome.

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.

In vivo effect of interferon-beta 1a on interleukin-12 and TGF-beta(1) cytokines in patients with relapsing-remitting multiple sclerosis.

We have studied in vivo effect of interferon-beta 1a (IFN-beta 1a) (6 MIU once weekly i.m.) on interleukin-12 (IL-12) and transforming growth factor-beta(1) (TGF-beta(1)) serum levels during 6 months of therapy in group of 20 patients with relapsing-remitting multiple sclerosis (MS). IL-12 and TGF-beta(1) concentrations were measured by enzyme linked immunoabsorbent assay (ELISA). There was a significant increase of IL-12 levels in MS patients in comparison with control group, suggesting a role of this cytokine in immunity of MS. We have also found a significant increase of TGF-beta(1) levels after 6 months of therapy with IFN-beta 1a, however, there was no in vivo effect of the therapy on IL-12 levels. The results suggest that IFN-beta 1a may exert its action through up- regulation and increase secretion of TGF-beta(1).

Early TNF-alpha levels correlate with ischaemic stroke severity.

OBJECTIVES: The study aimed to evaluate the levels of an important proinflammatory cytokine tumour necrosis factor-alpha (TNF-alpha) in cerebrospinal fluid (CSF) and serum in acute stroke and to study the relation between those and the neurological stroke severity and functional disability. MATERIAL AND METHODS: The investigations comprised 23 ischaemic stroke patients. CSF and blood samples were obtained 24 h after the onset of stroke, and stored until analysis. Patients were examined according to Scandinavian Stroke Scale (SSS) and to Barthel Index (BI). RESULTS: The patients displayed statistically significant high levels of TNF-alpha in CSF and sera within the first 24 h of stroke. These correlated significantly with SSS and BI scores calculated within the same interval, and 1 and 2 weeks later. CONCLUSION: Our results suggest the involvement of TNF-alpha in mechanisms of early stroke-induced inflammation and a predictive value of the initial TNF-alpha levels for the outcome of stroke.

Monocyte chemoattractant protein-1 is increased in the cerebrospinal fluid of patients with ischemic stroke.

BACKGROUND AND PURPOSE: Animal models of stroke have shown that focal cerebral ischemia results in an increased expression of several cytokines and chemokines that precedes leukocyte infiltration into ischemic lesions. The infiltrated leukocytes are thought to contribute to tissue injury in stroke. Monocyte chemoattractant protein-1 (MCP-1) may play an important role in monocyte/macrophage infiltration in stroke patients. METHODS: We studied MCP-1 level in sera and the cerebrospinal fluid of 23 ischemic stroke patients 24 hours after the onset of neurological symptoms and compared the results with 15 control patients with tension headache. The MCP-1 level was determined by ELISA. RESULTS: There was a significant increase of cerebrospinal fluid MCP-1 level in the studied stroke patients in comparison with the control group. The serum level of MCP-1 did not differ from that of control patients. CONCLUSIONS: Our results suggest that MCP-1 may play a role in the inflammatory reaction during the early phase of ischemic stroke.

Biological markers to confirm diagnosis and monitor the therapy in multiple sclerosis patients.

In patients suspected of multiple sclerosis (MS), even in the case of MRI positive changes, cerebrospinal fluid (CSF) analysis is of great practical value. Until now, however, only IgG index, restricted oligoclonal IgG bands and the examination of IgG subclasses have been of practical value. The determination of other immunological markers is too expensive to be introduced into laboratory diagnostic standards in MS. However, the clinical trials should be monitored by a large set of markers of MS activity, including the estimation of anti MBP antibodies, presence of MBP material in the CSF and concentration of sVCAM-1, ICAM-1, PECAM-1 in CSF and serum.

Effect of cladribine treatment on beta-2 microglobulin and soluble intercellular adhesion molecule 1 (ICAM-1) in patients with multiple sclerosis.

beta-2 Microglobulin (beta 2M) is a low molecular weight protein located extracellularly and associated with class 1 antigens of the major histocompatibility complex and is considered a marker for disease activity in immune disorders. Cladribine (2-chloro-2-deoxyadenosine, 2-CDA) is a potent lymphocytotoxic agent under investigation in the treatment in MS patients. As beta 2M levels may indicate inflammatory events in CNS we determined CSF-beta 2M and serum beta 2M levels in patients with relapsing-remitting MS before and after cladribine treatment as well as in a control group. There was a significant beta 2M decrease in sera but not in CSF in MS patients after the cladribine treatment, associated with a slight but significant clinical improvement measured by Kurtzke's Expanded Disability Status Scale. We also found a significant decrease in sICAM-1 level in CSF but not in sera in MS patients. The data support a role of cladribine in MS therapy and deliver new information on cladribine immunological effects in MS patients.

IL-18 in patients with multiple sclerosis.

IL-18 is a cytokine which plays an important role in Th-1 response through its ability to induce IFN-gamma production in T cells and NK cells. The purpose of the study was to measure IL-18 levels in serum and CSF of 21 patients with the relapsing-remitting form of MS, 9 with active gadolinium enhancing lesions in MRI and 12 without enhancing lesions, and to compare results with control group consisting of 11 patients with diagnosis of neurasthenia and tension headache. IL-18 concentration in the CSF and sera was measured by ELISA. We found a highly significant increase of both IL-18 CSF and serum levels in MS patients in comparison with the control group. In patients with active MRI lesions the levels of IL-18 in CSF and serum were significantly higher in comparison with the levels found in patients without enhancing lesions. The results suggest involvement of IL-18 in immunopathogenesis of MS especially in the active stages of the disease.

[Tumor necrosis factor alpha (TNF-alpha) in patients with ischemic stroke]. / Czynnik martwicy nowotworu alfa (TNF-alfa) u chorych z udarem niedokrwiennym mózgu.

Tumour necrosis factor alpha (TNF-alpha) is a proinflammatory cytokine. Stroke induces a rapid increase in TNF-alpha levels within and around the focus of damaged brain. The aim of our study was to evaluate, whether patients with stroke differ from control patients in the concentrations of TNF-alpha in cerebrospinal fluid and serum. We studied TNF-alpha levels in cerebrospinal fluid and serum in 30 patients with stroke within 24 h after onset of neurological signs and in 15 patients of control group with the diagnosis of tension headache and neurasthenia. In patients with stroke the levels of TNF-alpha in the cerebrospinal fluid and serum were significantly higher in comparison with control group. The results of our study may suggest the overproduction of TNF-alpha during first twenty-four hours of stroke.

[Surface CD2, CD4, CD8 markers and IL-2 and TNF-alpha cytokines in amyotrophic lateral sclerosis]. / Markery powierzchniowe CD2, CD4, CD8 oraz cytokiny: IL-2 i TNF-alpha w stwardnieniu bocznym zanikowym.

The cause of amyotrophic lateral sclerosis is still unknown. In the paper CD2, CD4 and CD8 markers on mononuclear cells as well as levels of TNF-alpha and IL-2 in sera from 15 patients with ALS were evaluated. There was a significant increase of TNF-alpha in sera of ALS patients in comparison with control group. This is the first such observation. It supports the concept that immune mechanisms may play a role in the pathogenesis of ALS.

The levels of TNF-alpha in cerebrospinal fluid and serum do not correlate with the counts of the white blood cells in acute phase of ischaemic stroke.

Stroke-induced inflammatory reaction, which leads to invasion of leukocytes into the evolving brain infarct, seems to play a key role in the deterioration of brain ischaemic impairment. We have studied CSF and serum levels of tumour necrosis factor-alpha (TNF-alpha), the potent proinflammatory cytokine, and peripheral white blood cells (WBC) counts in patients within the first 24 hours of ischaemic stroke. TNF-alpha levels in CSF and serum as well as WBC counts were increased. There was no correlation between TNF-alpha levels either in CSF and serum or in WBC counts. The results of our study suggest that increased CSF TNF-alpha levels may represent acute intracerebral inflammation in stroke, whereas elevated levels of TNF-alpha in serum may reflect the peripheral proinflammatory state as well as stroke-induced systemic inflammatory reaction. Increased CSF and serum TNF-alpha levels do not correlate with the elevation of WBC counts, suggesting that TNF-alpha overexpression observed in early phase of stroke is not dependent on increased total number of peripheral leukocytes.

Tumour necrosis factor-alpha is increased in the cerebrospinal fluid and serum of ischaemic stroke patients and correlates with the volume of evolving brain infarct.

A growing body of evidence suggests the involvement of inflammatory mediators, including cytokines, in the development of ischaemic brain lesions. The aim of the present study was to investigate whether tumour necrosis factor-alpha (TNF-alpha), the proinflammatory cytokine, contributes to early pathophysiological mechanisms leading to brain damage as a consequence of acute stroke. We have studied TNF-alpha levels in cerebrospinal fluid (CSF) and serum in 23 stroke patients within the first 24 hours after ischaemic stroke, confirmed by computerized tomography of the brain (CT). The control group consisted of 15 patients with the diagnosis of tension headache and neurasthenia. In stroke patients the levels of TNF-alpha both in CSF and serum were significantly higher in comparison with the control group. The positive correlation between the levels of TNF-alpha in CSF and serum of the studied patients has been observed. Furthermore, a positive correlation between both TNF-alpha levels in CSF and serum and the volume of evolving brain infarct have been shown.

[Viral infections in the pathogenesis of multiple sclerosis]. / Zakazenia wirusowe w patogenezie stwardnienia rozsianego.

In the paper the current opinion on the role of viral infections in the pathogenesis of multiple sclerosis is presented. The results of epidemiological and serological studies are discussed as well as the results of viral isolation attempts and the search for virus structures in CNS of MS patients. Relation between viral infections and MS exacerbations and postulated mechanisms of virus-induced demyelination is described.

[Chemokines MIP-1 and MCP-1 and patients with multiple sclerosis treated with interferon beta-1a]. / Chemokiny: MIP-1 alpha oraz MCP-1 u pacjentów ze stwardnieniem rozsianym leczonych interferonem beta-1a.

Chemokines: MCP-1 and MIP-1 alpha may play an important role in the pathogenesis of multiple sclerosis, influencing migration of lymphocytes to the CNS. One of possible mechanisms of interferon beta action may be an effect on chemokines. We measured MCP-1 and MIP-1 alpha chemokines in sera of 24 patients with MS treated with interferon beta-1a before and after 3 months of therapy and in 15 control patients. There was a significant increase of MIP-1 alpha concentration in sera of MS patients in comparison with control group. After 3 months of therapy with interferon beta-1a, MIP-1 alpha and MCP-1 levels did not differ from the values before therapy. Investigations will be continued after longer time of treatment with interferon beta.

[Interferon beta and copolymer-1: mechanism of action and clinical effects in multiple sclerosis]. / Interferon beta oraz copolimer-1: mechanizm dzialania oraz efekty kliniczne w stwardnieniu rozsianym.

In the paper the review of clinical trials with interferon beta and copolimer-1 in the treatment of multiple sclerosis was presented. The effect of interferon beta and copolimer-1 on relapse frequency, disability and MRI activity has been described. The mechanism of action of interferon beta and copolimer-1 in MS was discussed.

[The effect of cladribine treatment on beta-2 microglobin in the cerebrospinal fluid and serum of patients with multiple sclerosis]. / Wplyw 2-chlorodeoksyadenozyny (kladrybiny) na stezenie beta 2-mikroglobuliny w plynie mózgowo-rdzeniowym i surowicy u chorych ze stwardnieniem rozsianym.

Multiple sclerosis (MS) is the most frequent demyelinating disease of the central nervous system (CNS). Lymphocytes seem to play a crucial role in the pathogenesis of the disorder. They are rich in, among others, beta-2Microglobulin (beta 2M)--a low molecular weight protein located extracellularly and associated with class 1 antigens of the major histocompatibility complex. beta-2M is considered as a marker for disease activity in immune disorders. Its precise role in pathology remains still unknown, but there is evidence that it may be involved in lymphocyte activation. Cladribine (2-chloro-2-deoxyadenosine, 2-CDA) is a potent lymphocytotoxic agent under investigation in the treatment in MS patients, earlier used in hairy-cell-leukemia therapy. Previous studies in MS populations showed beta 2-microglobulin to be moderately increased. Suspecting that beta 2M levels might indicate inflammatory events in CNS we determined CSF-beta 2M and serum beta 2M concentration in patients with relapsing-remitting MS (n = 15) before and after cladribine treatment as well as in a control group diagnosed as tension type headache (n = 10). There was a significant decrease in the CSF and sera beta 2M level in MS patients after cladribine treatment, associated with a slight but significant clinical improvement measured by Kurtzke's Expanded Disability Status Scale. We conclude that beta 2M is a sensitive marker of the CDA influence on the immune system in MS patients; however, increase in CSF and sera beta 2M is not specific as there was no statistically significant difference between MS and control patients.

[Immunological markers of disease activity in the course of 2-CDA treatment of multiple sclerosis]. / Immunologiczne markery aktywnosci choroby w przebiegu leczenia kladrybina stwardnienia rozsianego.

52 clinically definite multiple sclerosis (MS) patients were treated with subcutaneous injection of 5 mg 2-CDA in 5 consecutive days. The injection courses were repeated 6 times in one month interval. The MRI pattern and immunological markers were studied in serum and CSF before and after 6 months of treatment. The obtained results suggest that treatment with 2-CDA has not any significant effect on humoral immunological events in multiple sclerosis, what is in contrast to some normalization of cellular immunopathological processes.