Biomedical subjects

V Ozenci

Publications and source records attributed to V Ozenci.

23 records · Page 2Linked to original sources

PubMed1999

Increased levels of circulating acetylcholine receptor (AChR)-reactive IL-10-secreting cells are characteristic for myasthenia gravis (MG).

Antibodies to the nicotinic AChR are pivotal in the immunopathogenesis of MG. Cytokines produced by T-helper cells are important regulators of humoral immune responses. IL-10 is considered an anti-inflammatory cytokine, but it promotes B cell activation and worsens experimental autoimmune MG in Lewis rats, an experimental model of MG. To study IL-10 and, as a control, interferon-gamma (IFN-gamma) in MG, we used an enzyme-linked immunospot (ELISPOT) assay, thereby assessing numbers of blood mononuclear cells (MNC) secreting IL-10 and IFN-gamma spontaneously and after stimulation with AChR. Low numbers of IL-10-secreting cells were regularly found in peripheral blood from patients with MG as well as in controls with other neurological diseases and healthy subjects. However, only MG patients had elevated blood levels of AChR-reactive IL-10- and IFN-gamma-secreting cells. The MG patients showed no responses to the control autoantigen myelin basic protein, underlining the specificity of the IL-10 and IFN-gamma responses. Immunosuppressive treatment reduced numbers of AChR-reactive IFN-gamma-secreting cells but increased the numbers of IL-10-secreting cells. The numbers of IL-10-secreting cells tended to be higher in patients with generalized versus ocular MG, further suggesting that the augmented IL-10 responses may be important in the pathogenesis and perpetuation of MG.

Adult↗

PubMed1999

Multiple sclerosis: levels of interleukin-10-secreting blood mononuclear cells are low in untreated patients but augmented during interferon-beta-1b treatment.

The cytokine interleukin (IL)-10 has immune response down-regulatory properties, which include suppression of the synthesis of pro-inflammatory cytokines such as interferon (IFN)-gamma and of major histocompatibility complex (MHC) class II expression on monocytes. To further elucidate the involvement of IL-10 in multiple sclerosis (MS), an enzyme-linked immunospot assay was adopted to enumerate IL-10-secreting mononuclear cells (MNC) in peripheral blood. IFN-gamma secreting MNC were detected in parallel. Levels of IL-10-secreting cells were lower in patients with MS compared with other neurological diseases (OND) and healthy subjects. This difference was seen only in patients with untreated MS, and not in those undergoing treatment with IFN-beta-1b. No differences were observed when subgrouping the patients with MS regarding clinical phase (exacerbation, remission, secondary progression), duration of MS or disability status. Levels of IFN-gamma-secreting blood MNC did not differ in patients with MS, irrespective of treatment with IFN-beta-1b, compared with OND and healthy subjects. Patients with MS, but not the two groups of controls, had elevated numbers of IL-10- and IFN-gamma-secreting cells upon stimulation with MBP compared with culture in the absence of antigen. The data suggest that IL-10 is decreased in MS and that treatment resulting in its up-regulation beneficially influence the disease.

Adult↗

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

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↗

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↗