| 1. |
- Huang, WX, et al.
(författare)
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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
- 1999
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Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 5:5, s. 342-348
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Tidskriftsartikel (refereegranskat)abstract
- 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-g), tumor necrosis factor alpha (TNF-a), 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 (P50.0001). TNF-a 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.
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| 2. |
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| 3. |
- Kivisakk, P, et al.
(författare)
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Neutralising and binding anti-interferon-beta-I b (IFN-beta-I b) antibodies during IFN-beta-I b treatment of multiple sclerosis
- 1997
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Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 3:3, s. 184-190
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Tidskriftsartikel (refereegranskat)abstract
- Interferon-β-1b (IFN-β-1b) is an immunomodulatory therapy of multiple sclerosis (MS), reducing the numbers and severity of exacerbations and the total lesion load measured by magnetic resonance imaging of the brain. The benefits of IFN-β-1b could be hampered by the development of neutralising antibodies against the compound. Our results confirmed earlier studies, showing that 42% of MS patients treated with IFN-β-1b for more than 3 months had developed neutralising antibodies. The occurrence of binding anti-IFN-β-1b antibodies, presently not believed to impede the clinical efficacy of IFN-β-1b, were demonstrated by an immunoassay in some patients already after I month of treatment and in 78% after 3 months. The development of binding antibodies seemed to be an early phenomenon, preceding the appearance of neutralising antibodies. Antibodies crossreacting with IFN-β-1a and natural IFN-β were also found in a majority of IFN-β-1b treated patients with high titres of binding antibodies. Employing a solid-phase enzyme-linked immunospot (ELISPOT) assay, 68% of MS patients treated with IFN-β-1b for 1 -23 months had elevated numbers of anti-IFN-β-1b-antibody secreting cells in blood, compared to 18% of untreated MS patients and 20% among patients with other neurological diseases. Thus, our findings confirm that IFN-β-1 b is immunogenic in MS patients. High levels of anti-IFN-β-1b antibody secreting cells were, however, also found in two untreated control patients with inflammatory diseases, suggesting that anti-IFN-β-1b antibodies might also occur spontaneously.
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| 4. |
- Link, H
(författare)
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The cytokine storm in multiple sclerosis
- 1998
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Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 4:1, s. 12-15
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Tidskriftsartikel (refereegranskat)
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| 5. |
- Mata, S, et al.
(författare)
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Multiple sclerosis is associated with enhanced B cell responses to the ganglioside GD1a
- 1999
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Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 5:6, s. 379-388
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Tidskriftsartikel (refereegranskat)abstract
- 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 JgM antibody titers and absorbances to the three major gangliosides GDIa, GD l b and GM, 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 patient (P <0.05) presented elevated IgG antibody titers to GD) a in serum compared to 9% of patient with OND. Six (40%) of the patient with malignant MS had elevated serum IgG antibody titers to GD) a compared to one (6%) of th e patient with benign MS (P <0.04). In CSF, elevated IgG antibody titers to GDIa were measured in 13% of MS and 20% of ON patient compared to 4% of patient with OND (P < 0.03 and P < 0.02, respectively). The augmented IgG response to GD) a in serum also separated MS from Guillain-Barr6 syndrome. Compared to OND increased JgM absorbances to sulfatides and cardiolipin were observed in CSF of patient with MS, but also in AM. Elevated IgG antibody titers to myelin proteins were found more often in MS patient' serum and MS, ON and AM patient' CSF compared to OND. The data implicate that among the multitude of enhanced B-cell responses occurring in MS and ON, that directed to GD I a is common and more discriminative, and should be evaluated in future MS treatment studies.
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| 6. |
- Matusevicius, D, et al.
(författare)
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Interleukin-17 mRNA expression in blood and CSF mononuclear cells is augmented in multiple sclerosis
- 1999
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Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 5:2, s. 101-104
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 7. |
- Söderström, M, et al.
(författare)
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Expression of IFN-gamma, IL-4, and TGF-beta in multiple sclerosis in relation to HLA-Dw2 phenotype and stage of disease
- 1995
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Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 1:3, s. 173-80
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Tidskriftsartikel (refereegranskat)abstract
- Multiple sclerosis (MS) is associated with upregulation of both proinflammatory (interferonγ, IFNγ) and immunosuppressive (transforming growth factorβ, TGFβ) cytokines. To examine a possible relation between the MS-related HLA haplotype Dw2 and cytokine prof iles, we used in situ hybridization with labeled cDNA oligonucleotide probes to detect transcripts of the T helper type I (ThI) cell related IFNγ, the Th2 cell related interleukin-4 (IL-4) and of TGFβ in blood and cerebrospinal fluid (CSF) mononuclear cells from 62 patients with MS. Compared to patients with other neurological diseases and healthy controls, MS patients had elevated numbers of IFNγ, IL-4 and TGFβ mRNA expressing cells in blood and further augmented in CSF. Although several HLA-Dw2-positive individuals showed very high numbers of cells expressing these cytokines, no significant difference was found in comparison with Dw2-negative patients. However, expression of IL-4 and TGFβ mRNA was significantly increased in patients with shorter duration and minor disability and, for IL-4, in patients still in the relapsing-remitting phase compared to patients with secondary chronic progressive MS. Surprisingly, these changes which favour a beneficial, disease-downregulating effect of IL-4 and TGFβ in MS, were found to be confined to HLA-Dw2-positive patients. Our findings suggest that the HLA phenotype does not influence the overall level of immune reactivity in MS, but may distinguish subgroups characterized by particular cytokine expression patterns.
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