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H Link

Publications and source records attributed to H Link.

At least 109 records · Page 6Linked to original sources
PubMed1999

Levels of interleukin-15-expressing blood mononuclear cells are elevated in multiple sclerosis.

Interleukin-15 (IL-15) is a novel IL-2-like cytokine expressed by cells of the monocyte/macrophage and epithelial lineages. Cytokines might be involved in the pathogenesis of multiple sclerosis (MS). Using immunocytochemistry, we analysed spontaneous expression of IL-15 by peripheral blood (PB) and cerebrospinal fluid (CSF) mononuclear cells (MNC) from patients with MS, other neurological diseases (OND) and healthy controls. IL-15- positive peripheral blood mononuclear cells (PBMNC) were elevated in patients with MS compared to healthy controls (P < 0.05). The elevation of IL-15- positive PBMNC was restricted to patients with chronic progressive MS and not observed in patients studied during the relapsing-remitting phase of MS. The numbers of IL-15- expressing PBMNC correlated with the duration and disability of MS (r = 0.45, P < 0.001, and r = 0.39, P < 0.01, respectively). IL-15 was undetectable in CSF MNC, and ELISA showed low CSF levels of IL-15 in occasional patients with MS and OND. IL-15 is a potent growth factor for gammadelta T cells, but there was no correlation between IL-15 expression by PBMNC and percentage of gammadelta T cells in blood from the MS patients. Together, these data demonstrate that IL-15 expression by PBMNC is upregulated in the chronic stage of MS.

Adolescent↗
PubMed1999

High levels of IL-10 secreting cells are present in blood in cerebrovascular diseases.

Ischemic stroke is associated with altered systemic immune responses both early after the onset and in the recovery phase. Interleukin (IL)-10, a Th2 related cytokine, has multiple effects on different cell types, including T and B lymphocytes, monocytes, neutrophils and mast cells. IL-4 is another Th2 cytokine that inhibits the synthesis of pro-inflammatory cytokines by Th1 clones. We used enzyme-linked immunospot assays to detect and enumerate blood mononuclear cells (MNC) secreting IL-10 and IL-4 spontaneously as well as after stimulation with myelin basic protein (MBP), considered to be an autoantigen of possible pathogenic importance in, for example, multiple sclerosis, to evaluate the involvement of anti-inflammatory cytokines in ischemic stroke. All patients with ischemic stroke and cerebral hemorrhage had strongly elevated numbers of IL-10 secreting blood MNC compared with healthy individuals. Numbers of MBP-reactive IL-10 secreting blood MNC were also elevated in a proportion of the patients with stroke and hemorrhage. Levels of IL-4 secreting blood MNC did not differ in ischemic stroke versus healthy individuals. The anti-inflammatory IL-10 could play a pivotal role in ischemic stroke as well as cerebral hemorrhage.

Acute-Phase Reaction↗
PubMed1999

A novel mechanism for cytokine regulation: screening, selection, and characterization of anticytokine monoclonal and polyclonal autoantibodies.

We have recently described an immunoregulatory mechanism involving release of neutralizing autoantibodies (Aab) to cytokines during bacterial infections. Intraperitoneal inoculation of Haemophilus influenzae type b (Hib) into Sprague-Dawley rats resulted in high levels of inflammatory mediators early after infection. Increased titers of cytokine Aab were observed, with a peak at day 7. We cloned Aab-producing B cells. Screening of the clones with five different cytokines resulted in detection of Aab-producing clones reactive with each cytokine. After repeated subcloning, monoclonal Aab (mAab) were selected and characterized for their specificity, isotypes, and affinities. To elucidate regulatory importance, mAab to interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) dose-dependently inhibited IFN-gamma-induced MHC expression by peritoneal macrophages and TNF-alpha-induced thymocyte proliferation, respectively. Fab fragments exhibited binding and neutralizing effects, confirming specificities. Cross-reactivity with other rat cytokines was excluded. Pools of clones containing several mAab to each cytokine were obtained and served as polyclonal Aab. The relative affinity of the Aab was determined and found to be of high index. The characterized Aab were tested in methodologic assays for cytokine detection, revealing that some Aab were useful in a cell release capturing (CRC) ELISA.

Animals↗
PubMed1999

High numbers of perforin mRNA expressing CSF cells in multiple sclerosis patients with gadolinium-enhancing brain MRI lesions.

Enhanced expression of pro- and anti-inflammatory cytokines is a common finding in MS, but attempts to correlate cytokine expression with disease activity have produced conflicting results. In this paper, gadolinium-(Gd-)enhancing lesions on brain MRI were used as markers for active inflammation in patients with MS not treated with any immunomodulatory drugs. In parallel, in situ hybridization was used to detect blood and cerebrospinal fluid (CSF) mononuclear cells (MNC) expressing cytokine mRNA. An association was observed between numbers of perforin mRNA expressing CSF MNC and numbers of Gd-enhancing brain MRI lesions. Perforin mRNA expressing CSF MNC were not detected in any of the patients lacking active lesions on brain MRI. The expression of tumor necrosis factor-alpha, interleukin-10 (IL-10) and IL-12 mRNA in CSF MNC did not differ between MS patients with and without active MRI lesions. Based on the present finding, a role for perforin in the disruption of the blood-brain barrier in MS can be hypothesized.

Adult↗
PubMed1999

First hospital-admission rate as an epidemiological indicator for patients with multiple sclerosis in Stockholm, 1984-1993.

OBJECTIVES: To evaluate the first hospital-admission patients with multiple sclerosis (MS) in the population. MATERIAL AND METHODS: By using the data from hospital discharge registry of MS diagnosis in Stockholm during 1984-1993, we calculated rates of first hospital-admission patients with MS in the population and evaluated the temporal trend of the rates during the study period. RESULTS: There were 719 first hospital-admission patients with MS corresponding to 1556 admissions. The mean age at the first admission was nearly the same for male patients (44.3 years, SD: 12.9) and for female patients (44.6 years, SD: 13.7). The mean annual rate of first hospital-admission patients with MS was 4.46 per 100,000 person-years. The sex rate ratio of first hospital-admission patients with MS between females and males was 2.19:1. CONCLUSION: The first hospital-admission rate of MS could be used as an epidemiological indicator which is useful in planning of hospital service for MS patients.

Adolescent↗
PubMed1999

A new cell enzyme-linked immunosorbent assay demonstrates gamma interferon suppression by beta interferon in multiple sclerosis.

Multiple sclerosis (MS) is a demyelinating disorder of the central nervous system of unknown etiology. Immune mechanisms involving the proinflammatory cytokine gamma interferon (IFN-gamma) are believed to play an important role in the pathogenesis of MS. IFN-beta-1b has been introduced as a treatment for MS and was found to reduce the number and severity of clinical exacerbations. To examine the influence of IFN-beta-1b on myelin basic protein (MBP)-specific and phytohemagglutinin-induced IFN-gamma production, we developed a cell-released capturing enzyme-linked immunosorbent assay (CRC-ELISA), which rapidly measures spontaneous and antigen- or mitogen-induced cellular IFN-gamma production. CRC-ELISA documented a significant MBP-specific T-cell response in the blood of untreated MS patients, as assessed by IFN-gamma production. This response was suppressed in MS patients treated with IFN-beta-1b. The present work confirms in vivo the in vitro suppressive effects of IFN-beta-1b on IFN-gamma production in MS. Moreover, it provides a powerful new technique for detection of cytokines.

Adult↗
PubMed1999

Neutralization of macrophage inflammatory protein 2 (MIP-2) and MIP-1alpha attenuates neutrophil recruitment in the central nervous system during experimental bacterial meningitis.

Chemokines are low-molecular-weight chemotactic cytokines that have been shown to play a central role in the perivascular transmigration and accumulation of specific subsets of leukocytes at sites of tissue damage. Using in situ hybridization (ISH), we investigated the mRNA induction of macrophage inflammatory protein 2 (MIP-2), MIP-1alpha, monocyte chemoattractant protein 1 (MCP-1), and RANTES. Challenge of infant rats' brains with Haemophilus influenzae type b intraperitoneally resulted in the time-dependent expression of MIP-2, MIP-1alpha, MCP-1, and RANTES, which was maximal 24 to 48 h postinoculation. Immunohistochemistry showed significant increases in neutrophils and macrophages infiltrating the meninges, the ventricular system, and the periventricular area. The kinetics of MIP-2, MIP-1alpha, MCP-1, and RANTES mRNA expression paralleled those of the recruitment of inflammatory cells and disease severity. Administration of anti-MIP-2 or anti-MIP-1alpha antibodies (Abs) resulted in significant reduction of neutrophils. Administration of anti-MCP-1 Abs significantly decreased macrophage infiltration. Combined studies of ISH and immunohistochemistry showed that MIP-2- and MIP-1alpha-positive cells were neutrophils and macrophages. MCP-1-positive cells were neutrophils, macrophages, and astrocytes. Expression of RANTES was localized predominantly to resident astrocytes and microglia. The present study indicates that blocking of MIP-2 or MIP-1alpha bioactivity in vivo results in decreased neutrophil influx. These data are also the first demonstration that the C-C chemokine MIP-1alpha is involved in neutrophil recruitment in vivo.

Animals↗
PubMed1999

Levels of gamma interferon and interleukin-4 are inversely related to the levels of their corresponding autoantibodies in patients with lower respiratory tract infection.

To study the involvement of cytokines and their corresponding autoantibodies (Aabs) in inflammatory mechanisms in patients with lower respiratory tract infections, blood samples were taken from patients at the time of admission to the hospital and before treatment. Cell-released capturing enzyme-linked immunosorbent assay was used to measure the levels of gamma interferon (IFN-gamma) and interleukin-4 (IL-4) produced spontaneously by peripheral mononuclear cells (PMNC). ELISA was used to measure Aabs to these cytokines in sera. The levels of both cytokines were inversely related to the levels of their corresponding Aabs. While a high level of IFN-gamma was observed together with a low level of anti-IFN-gamma Aab, decreased IL-4 levels were observed with increased levels of Aabs to IL-4. Immunoglobulins were purified, digested to obtain Fab fragments, and tested for specificity and cross-reactivity. The Aabs and their Fab fragments were tested in cytokine biological assays and showed neutralizing effects. Our data demonstrated increased levels of the proinflammatory cytokine IFN-gamma and decreased release of the anti-inflammatory cytokine IL-4 during early presentation of lower respiratory tract infection. The levels of these cytokines were inversely related to the levels of their corresponding Aabs that exhibited regulatory effects on the cytokine biological function in vitro.

Adult↗
PubMed1999

Increased IL-1beta, IL-8, and IL-17 mRNA expression in blood mononuclear cells observed in a prospective ischemic stroke study.

BACKGROUND AND PURPOSE: Ischemic brain injury secondary to arterial occlusion is characterized by acute local inflammation, which involves accumulation of polymorphonuclear neutrophils (PMN). Factors that influence the recruitment of PMN could represent new therapeutic targets in acute stroke. In this prospective study we evaluated numbers of peripheral blood mononuclear cells (PBMC) expressing mRNA for interleukin (IL)-1beta, IL-8, and IL-17 and macrophage inflammatory protein-1alpha (MIP-1alpha) after ischemic stroke. METHODS: Peripheral blood was obtained on days 1 to 3, 4 to 10, and 20 to 31 after onset of symptoms. In situ hybridization with radiolabeled synthetic oligonucleotide probes was adopted to measure cytokine mRNA expression in PBMC. Plasma and cerebrospinal fluid levels of IL-8 were measured by an enzyme-linked immunosorbent assay. RESULTS: Most patients with ischemic stroke had clearly elevated numbers of IL-1beta, IL-8, and IL-17 mRNA expressing PBMC 1 to 3 days after onset of symptoms compared with healthy individuals (P<0. 0001 for all comparisons). At follow-up after 20 to 31 days, numbers of IL-8 mRNA expressing PBMC were lower than during the acute stage (P<0.001), but only IL-1beta and IL-17 mRNA expression had returned to the level of the healthy individuals. Numbers of MIP-1alpha mRNA expressing PBMC did not differ between patients with ischemic stroke and healthy individuals at any time point. A correlation was observed between numbers of IL-1beta, IL-8, and IL-17 mRNA expressing PBMC and the degree of neurological impairment as measured by the Scandinavian Stroke Scale 1 to 3 days after onset of symptoms (r=0.5; P<0.01 for all correlations). CONCLUSIONS: A longitudinal study of patients with ischemic stroke revealed systemic increases of levels of IL-1beta, IL-8, and IL-17 that correlated with Scandinavian Stroke Scale scores. IL-8 levels were further increased in cerebrospinal fluid.

Aged↗
PubMed1999

Interleukin-17 mRNA expression in blood and CSF mononuclear cells is augmented in multiple sclerosis.

Myelin-directed autoimmunity is considered to play a key role in the pathogenesis of multiple sclerosis (MS). Increased production of both pro- and anti-inflammatory cytokines is a common finding in MS. Interleukin-17 (IL-17) is a recently described cytokine produced in humans almost exclusively by activated memory T cells, which can induce the production of proinflammatory cytokines and chemokines from parenchymal cells and macrophages. In situ hybridisation with synthetic oligonucleotide probes was adopted to detect and enumerate IL-17 mRNA expressing mononuclear cells (MNC) in blood and cerebrospinal fluid (CSF) from patients with MS and control individuals. Numbers of IL-17 mRNA expressing blood MNC were higher in patients with MS and acute aseptic meningoencephalitis (AM) compared to healthy individuals. Higher numbers of IL-17 mRNA expressing blood MNC were detected in MS patients examined during clinical exacerbation compared to remission. Patients with MS had higher numbers of IL-17 mRNA expressing MNC in CSF compared to blood. This increase in numbers of IL-17 mRNA expressing MNC in CSF was not observed in patients with AM. Our results thus demonstrate increased numbers of IL-17 mRNA expressing MNC in MS with higher numbers in CSF than blood, and with the highest numbers in blood during clinical exacerbations.

Adult↗
PubMed1999

Nasal administration of transforming growth factor-beta1 induces dendritic cells and inhibits protracted-relapsing experimental allergic encephalomyelitis.

Cytokines have a crucial role in initiation and perturbation of EAE that represents an animal model of multiple sclerosis (MS). Administration of transforming growth factor-beta1 (TGF-beta1) to EAE mice improves clinical EAE and prevents relapses by unknown mechanisms. Administering low doses of TGF-beta1 nasally, we confirmed that TGF-beta1 inhibited development and relapse of protracted-relapsing EAE (PR-EAE) in DA rats. Infiltration of CD4+ T-cells and macrophages within the central nervous system was clearly reduced, while proliferation and IFN-gamma secretion of mononuclear cells (MNC) was augmented in TGF-beta1-treated EAE rats compared to PBS-treated control EAE rats. TGF-beta1 administered nasally also increased nitric oxide production and CD4+ T cell apoptosis. TGF-beta1 treated rats showed augmented proliferation of dendritic cells (DC) compared to MNC. These data imply that low doses of TGF-beta1 given by the nasal route prevent PR-EAE and upregulate DC functions that may be involved for disease prevention.

Administration, Intranasal↗
PubMed1999

Cytokine analysis in multiple sclerosis by competitive RT - PCR: A decreased expression of IL-10 and an increased expression of TNF-alpha in chronic progression.

Multiple sclerosis (MS) is an inflammatory, demyelinating disease that is specific to the central nervous system. Cytokines are thought to be key mediators of the autoimmune attack against central nervous system myelin in MS. To investigate the involvement of cytokines in MS, the mRNA levels of interferon gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), interleukin-4 (IL-4) and interleukin-10 (IL-10) in peripheral blood mononuclear cells without stimulation in vitro were quantified by a competitive reverse transcription polymerase chain reaction technique. The level of IL-10 specific mRNA was significantly decreased in 47 MS patients compared with 42 healthy controls (P<0.0001). TNF-alpha was significantly increased in MS patients compared with healthy controls (P=0.014), especially in the patients with chronic progressive MS (P=0.0003). Thus we conclude that there are significant in vivo alterations in cytokine gene expression in the periphery in MS.

Adult↗
PubMed1999

Multiple sclerosis is associated with enhanced B cell responses to the ganglioside GD1a.

The occurrence and role of autoantibodies to gangliosides and other lipid-containing components of the central nervous system in Multiple Sclerosis (MS) are unsettled. Using sensitive ELISAs, we measured IgG and IgM antibody titers and absorbances to the three major gangliosides GD1a, GD1b and GM1, and to sulfatides, cardiolipin and myelin proteins in paired serum and cerebrospinal fluid (CSF) from patients with untreated MS, optic neuritis (ON), acute aseptic meningo-encephalitis (AM) and other neurological diseases (OND). Twenty-three per cent of 30 MS (P<0.04) and 18% of 32 ON patients (P<0.05) presented elevated IgG antibody titers to GD1a in serum compared to 9% of patients with OND. Six (40%) of the patients with malignant MS had elevated serum IgG antibody titers to GD1a compared to one (6%) of the patients with benign MS (P<0.04). In CSF, elevated IgG antibody titers to GD1a were measured in 13% of MS and 20% of ON patients compared to 4% of patients with OND (P<0. 03 and P<0.02, respectively). The augmented IgG response to GD1a in serum also separated MS from Guillain-Barré syndrome. Compared to OND increased IgM absorbances to sulfatides and cardiolipin were observed in CSF of patients with MS, but also in AM. Elevated IgG antibody titers to myelin proteins were found more often in MS patients' serum and MS, ON and AM patients' CSF compared to OND. The data implicate that among the multitude of enhanced B-cell responses occurring in MS and ON, that directed to GD1a is common and more discriminative, and should be evaluated in future MS treatment studies.

Adult↗
PubMed1999

[Consultation per video-conferencing with regional hospitals: the MEDKOM project of the Hannover Medical University].

Consultations between doctors are necessary tools for decisions in diagnosis and treatment of patients. The mainstay is a sound communication between the participants, using verbal and audio-visual means. Usually clinical findings and imaging results are included. Using video technology with ISDN (integrated services digital network), such consulting can be performed across any distance. The department of hematology and oncology of the Medical School Hanover has introduced such a system in 1989 for conferencing with 12 regional hospitals and two private practices. It is now a well recognized and established system being applied for 270 sessions and for 1100 Patients per year. It is an integrated part of the co-operation, also allows medical education and quality improvement.

Computer Systems↗
PubMed1999

Induction of neutralizing autoantibodies to interferon-gamma in patients with polyneuropathy.

We previously demonstrated the induction of IFN-gamma in polyneuropathy patients associated with monoclonal gammopathy, but not in patients with presumably non-immunological types of neuropathy. We herein examined mechanism involving release of neutralizing autoantibodies (Aabs) to IFN-gamma in sera from those patients. In contrast to polyneuropathy patients with monoclonal gammopathy, patients with polyneuropathy of presumably non-immunological types showed increased production of neutralizing Aabs specific for IFN-gamma. These results demonstrate a role for autoimmunity in cytokine regulation. However, their association to the clinical manifestations of the disease requires further investigations, which are necessary for future consideration in therapeutic strategies.

Adult↗
PubMed1998

Cytokine and chemokine mRNA expressing cells in muscle tissues of experimental autoimmune myasthenia gravis.

In-situ hybridization with labeled oligonucleotide probes was applied to explore cytokine and chemokine mRNA expression in sections of striated muscle, the target organ in experimental autoimmune myasthenia gravis (EAMG), induced in Lewis rats by immunization with acetylcholine receptor (AChR) and complete Freund's adjuvant (CFA). A transient burst of TNF-alpha, IL-1beta and IL-6 mRNA expressing cells was detected during the early phase of EAMG. This cytokine pattern was related to muscular infiltration of macrophages. Levels of IL-4, IL-10, IFN-gamma, cytolysin and TGF-beta mRNA expressing cells were low and observed mainly during the early phase of EAMG. C-C chemokine RANTES, MCP, MIP-1alpha and MIP-2 mRNA expressing cells were not detected over the course of EAMG. The low and transient expression of cytokines in EAMG muscle tissues suggests that the immune effector responses are unlikely operated by infiltrating cells in muscle. Muscular infiltrations in EAMG are unlikely due to local accumulation of C-C chemokines.

Animals↗
PubMed1998

No evidence for elevated numbers of mononuclear cells expressing MCP-1 and RANTES mRNA in blood and CSF in multiple sclerosis.

The perivascular accumulation of mononuclear cells (MNC) in brain white matter is critical in the development of active lesions in multiple sclerosis (MS). Chemokines contribute to leukocyte recruitment by increasing the adhesiveness of integrins expressed on leukocytes and by promoting migration through endothelium and extracellular matrix. By using an in situ hybridization technique, it was possible to enumerate blood and CSF MNC expressing mRNA for the two CC chemokines monocyte chemoattractant protein-1 (MCP-1) and RANTES (regulated upon activation, normal T cells, expressed and secreted) in MS patients and controls. No differences in numbers of blood MNC expressing MCP-1 or RANTES could be found in MS patients compared to healthy individuals or patients with acute aseptic meningoencephalitis (AM). High numbers of CSF MNC expressing MCP-1 and RANTES were found in some MS patients, but also in patients with AM. This shows that elevated numbers of MCP-1 and RANTES mRNA expressing CSF MNC are not specific for the inflammatory process in MS. We conclude that there is no evidence for a systemic dysregulation of the CC chemokines MCP-1 and RANTES in MS.

Adult↗