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Biomedical subjects

A Nespolo

Publications and source records attributed to A Nespolo.

At least 19 recordsLinked to original sources

IL-10 production in multiple sclerosis patients, SLE patients and healthy controls: preliminary findings.

IL-10 is a cytokine with suppressive effects on (auto) antigen presentation and T-cell-mediated immune reactions, but is also capable of stimulating polyclonal IgG synthesis. Recent evidence suggests its involvement in multiple sclerosis (MS) and systemic lupus erythematosus (SLE). We assessed PBMNC IL-10 release in MS and SLE patients before and after in vivo prednisone or methylprednisolone treatment. The SLE patients showed a high level of IL-10 release by unstimulated PBMNCs, whereas the PHA-stimulated PBMNCs from MS patients produced large amounts of the cytokine.

Adult

Immunological monitoring of azathioprine treatment in multiple sclerosis patients.

Despite the longstanding clinical use of azathioprine as an immunosuppressive agent in multiple sclerosis, little is known about the action of this drug on a number of parameters of putative pathogenic relevance in the disease. Eleven patients with multiple sclerosis, treated with azathioprine 2.5-3 mg/kg per day, and six untreated patients were studied with serial blood sampling for 1 year. The following immunological parameters were investigated: peripheral blood lymphocyte subsets, natural killer activity, serum IgG, IgM, ICAM-1 and tumour necrosis factor alpha (TNF-alpha). The most relevant changes included a decrease in CD3- CD56+ cells, an increase in CD4+ CD45RA+ cells and a decrease in TNF-alpha levels only in treated patients, while no changes occurred in untreated patients over a 1-year period. The decrease in TNF-alpha levels and the increase in "suppressor-inducer" lymphocytes could reduce chronic inflammation in multiple sclerosis, and paralleled an overall favourable clinical response to azathioprine treatment in our patients.

Azathioprine

Effects of beta-IFN-1b treatment in MS patients on adhesion between PBMNCs, HUVECs and MS-HBECs: an in vivo and in vitro study.

The in vivo effects on the expression of adhesion molecules and on the adhesion between mononuclear cells and multiple sclerosis human brain endothelial cells (MS-HBECs) were investigated at the beginning of beta-IFN-1b treatment of MS patients. MS-HBECs were isolated from a surgical specimen obtained from an MS patient undergoing brain surgery for vascular aneurysm. 48 h after the first single administration of beta-IFN-1b, PBMNCs of 10 MS patients were analyzed for HLA-DR, CD11a, CD18 and VLA-4 expression and the adhesion between PBMNCs and both stimulated and unstimulated MS-HBECs evaluated. sICAM-1 and sVCAM-1 dosage in the serum of the patients was checked as well. The experiments were repeated using HUVECs in order to detect possible endothelial organ-specific differences. The experiments were also performed after six months of beta-INF-1b treatment on HUVECs. No significant effects on mononuclear cells/endothelium adhesion were detected at 48 h, but adhesion of PBMNCs to HUVECs decreased at six months. An increase in HLA-DR and VLA-4 and a decrease of CD18 was detected in monocytes. The serum level of sVCAM-1 increased at T2 and was still higher than at T0 at six months. The effect of the beta-IFN-1b treatment on both MS-HBECs and HUVECs, was selectively studied in vitro by testing the expression of cytokine-induced adhesion molecules HLA-DR, ICAM-1 and VCAM-1. The in vitro experiments confirmed that beta-IFN-1b is able to antagonize gamma-IFN-induced HLA-DR expression on MS human brain endothelial cells without relevant effects on VCAM-1 and ICAM-1.

Adult

The m-chlorophenylpiperazine test in cluster headache: a study on central serotoninergic activity.

The central serotoninergic agonist m-chlorophenylpiperazine (m-CPP) stimulates several 5HT receptor subtypes. It induces the release of both cortisol and prolactin (PRL). In this study we investigated central serotoninergic responsiveness in cluster headache by monitoring cortisol and PRL responses to m-CPP administration. Twenty-three patients with episodic cluster headache and 17 sex-matched and age-matched healthy subjects were studied. The cluster headache patients were tested during a cluster period, and none were receiving prophylaxis. A single oral dose of m-CPP, 0.5 mg/kg, was given at time 0. Blood samples were drawn at -30, 0, 30, 60, 90, 120, 150 and 180 min. PRL and cortisol levels were assayed in the samples. PRL and cortisol delta maxima (delta maximum = maximum response - baseline level at time 0/baseline level at time 0) were evaluated in each patient and mean values compared. Serum levels of m-CPP were detected by HPLC and correlated to hormonal responses. Reduced cortisol (p < 0.02) and increased PRL (p < 0.05) delta maxima were observed in cluster headache patients. Increased basal cortisol plasma levels (p < 0.05) and reduced basal PRL plasma levels (p = 0.06) also characterized cluster headache patients. This is the first study evaluating central serotoninergic responsiveness to m-CPP in cluster headache and these data suggest impaired central serotoninergic function in this pathology.

Case-Control Studies

Reduced adhesion of PBMNCs to endothelium in methylprednisolone-treated MS patients: preliminary results.

Methylprednisolone (MP) is a synthetic steroid commonly used in the treatment of multiple sclerosis (MS) relapses. It has a wide spectrum of activities on immune cells: it might also act by preventing mononuclear cell/endothelium adhesion. We studied adhesion phenomena between cultured human umbilical vein endothelial cells (HUVECs) and PBMNCs (CD45+, CD14+) from 6 MS patients treated in vivo with MP. We also studied fluctuations in CD11a and CD18 levels on lymphocytes and monocytes, as well as changes in serum sICAM-1 and sVCAM-1 concentrations. After MP treatment, PBMNCs adhesion to endothelium decreased at 3 h, while it went back to baseline levels at 24 h. A tendency to increase in both CD11a and CD18 on the surface of lymphocytes was detected, while an increase in serum sVCAM-1 was seen at 3 h.

Adult

Low serum interleukin-10 levels in multiple sclerosis: further evidence for decreased systemic immunosuppression?

Serum interleukin 10 (IL10) levels were assessed in patients with multiple sclerosis who were either in a stable or active clinical condition. The levels were compared with values in healthy controls. Lower IL10 levels than in controls were seen in multiple sclerosis patients, regardless of clinical disease activity. Low IL10 levels were also seen in patients with systemic lupus erythematosus. No clear-cut relationships emerged between IL10 levels and those of tumour necrosis factor alpha and transforming growth factor beta, or between IL10 and lymphocyte subsets in peripheral blood.

Adult

Intrathecal immunotherapy in CNS tumors disseminating via CSF: preliminary evaluation using different treatment schedules.

Eight patients affected by central nervous system tumours disseminating via cerebrospinal fluid received rIL-2 immunotherapy according to three different protocols involving intrathecal administration followed or not by systemic infusion. Immunological monitoring included serial evaluation of CSF leukocytes, CSF and peripheral blood CD3-CD56+ cells, and NK activity. The most marked rise in CSF leukocyte levels was induced by daily intrathecal rIL2 administration, which also induced increased PB NK activity. Systemic rIL2 infusion following intrathecal treatment maintained a high percentage of CSF CD3-CD56+ cells, but not CSF leukocytes at high levels. Clinical conditions improved after treatment in two patients, worsened in one and remained substantially unchanged in the remaining five. The side effects of intrathecal rIL2 treatment included fever, confusion, and seizures, and there were marked interindividual variations in the immunological response.

Adolescent

Analysis of HLA-class II DQA1, DQB1, DRB1 and DPB1 in Italian multiple sclerosis patients.

We studied the allelic constitution at the HLA class II DQA1, DQB1, DRB1 and DPB1 in 94 Italian multiple sclerosis (MS) patients and 98 controls. No significant increase in the frequency of DR2 alleles was detected among MS patients, as previously observed both in European and some Italian studies. A slight increase was found for the DQA1*0301 and DQB1*0602 alleles in the MS patients. No significant association was found with the glutamine residue at position 34 of the DQ alpha chain, which was noted previously in MS patients from northern Europe.

Alleles

Immunological monitoring and clinical evaluation in cyclophosphamide-treated progressive multiple sclerosis patients.

15 patients with progressive Multiple Sclerosis (MS) were treated by an induction Cyclophosphamide (CFX) schedule followed by bimonthly boosters over one year. Of the 14 patients who completed the trial, only two displayed worsening of neurological status. Cerebrospinal fluid (CSF) total protein, IgG/Alb ratio and IgG index decreased at 6 months and were still low at the end of the treatment. Pretreatment percentages of PB CD8+ and CD4+CD45RA+ lymphocytes were lower in MS patients in comparison with healthy controls. However, no significant shifts occurred in percentage of PB CD4+, CD4+CD45RA+, CD4+CD45RA-, CD8+ lymphocytes of MS patients during immunosuppressive treatment. The lack of changes in the investigated immunological parameters contrasts with the good clinical response and the low rate of serious side effects during this treatment schedule.

Antigens, CD

Immunological fluctuations during intrathecal immunotherapy in three patients affected by CNS tumours disseminating via CSF.

The immunological therapy of cancer has been proposed in a number of neoplasms (Borden, Sondel, 1989; Foon, 1989; Rosenberg, 1992) and has recently been adopted in the treatment of Central Nervous System (CNS) tumors in combination with conventional surgical and radiotherapeutical approach. In this context, loco-regional administration of immunomodulating agents (for instance in post-surgical cavity) allows to achieve much higher in situ concentrations than by systemic route. Since these treatments have potential adverse effects, careful assessment of clinical and immunological parameters in phase I trials is needed. CNS tumors disseminating via Cerebrospinal Fluid (CSF) pathways offer a stimulating opportunity for intrathecal immunotherapy. In this context, alpha-IFN and IL2 (alone or in combination with LAK cells) have been employed either loco-regionally or intrathecally (Merchant, Mc Vicar, Merchant & Young, 1992; Schiller, Hank, Storer, Borchert, Moore, Albertini, Bechhofer, Wesley, Brown, Bastin & Sondel, 1993). The rationale for the use of both these substances includes the known anti-tumor action of alpha-IFN (Mahaley, Urso, Whaley, Blue, Williams, Guaspari & Selker, 1985; Nagai, 1988) and the ability of r-IL2 to generate activated cells effective in lysing tumor cell targets (Hayes, Moore, Pierz, Chen, Da Rosso, Nirenberg & Allen, 1993). We treated 3 patients (2 affected by disseminating cerebellar medulloblastoma, 1 by disseminating thalamic glioblastoma) by intrathecal r-IL2 via recervoir. In the first 2 patients, this treatment was preceded by alpha-IFN (also intrathecally). Monitoring of immunological effects of the treatment schedule involved kinetics of CSF and serum TNF-alpha, IL2s and IL2R during the first day of r-IL2 treatment, as well as on day +2 and +4 of both r-IL2 cycles, and assessment of CSF cells, protein and CSF and PB NK cell activity and CD3-CD56+ cells during the course of all treatment cycles. We also assessed clinical and neuroradiological effects of immunotherapy.

Adult

High-dose methylprednisolone treatment-induced changes in immunological parameters in progressive MS patients.

The effect of High-Dose Methylprednisolone (HD-MP) treatment on Peripheral Blood (PB) and Cerebrospinal Fluid (CSF) immune parameters was investigated in 9 patients with relapsing-progressive Multiple Sclerosis (MS). Short-time effects included reduction of the percentage of CD3+, CD4+ and CD4+CD45RA+ PB lymphocytes and increase in CD3-CD56+ cells. At the end of the treatment, only increase in PB CD19+ and in CSF CD8+, CD8+CD28+ and decrease of CSF CD4+CD45RA- and serum IL2R levels were observed. No changes in CD11a+CD4+, CD18+CD14+ PB cells were observed after treatment. The results further stress the complex and multifaceted action of HD-MP on immune parameters.

Adult

Phenotype analysis of unstimulated lymphocytes and anti-CD3-stimulated proliferating T-cells from cerebrospinal fluid and peripheral blood in patients with multiple sclerosis and other neurological diseases.

In 15 patients with multiple sclerosis (MS) and in 11 patients with other neurological diseases (OND), the phenotype of fresh unstimulated CSF and PB mononuclear cells and of "in vitro" expanded T-cells was studied by monoclonal antibody stain and cytofluorimeter analysis. A compartment-specific decrease of CD8+Leu8+ and CD8+Leu8- cells in CSF was detected; moreover, lower levels of CD8+Leu8- cells were seen in MS than in OND patients, both in CSF and in PB. Although the percentages of unstimulated CSF CD4+ cells did not differ between MS and OND, a higher proportion of "in vitro" expanded CD4+ T-cells was obtained from MS patients than from OND. Among MS patients, T-cell growth was very scarce or absent in those sampled during relapses. The results suggest alterations both within the CD4+ "helper" and the CD8+ "suppressor-cytotoxic" populations in the CSF of MS patients, and stress the relevance of functional analysis in conjunction with phenotype studies.

Adult

Physical effort-induced changes in immune parameters.

Physical stress induces changes in immune system parameters; these changes depend on effort schedule and are influenced by customary training. The mechanisms whereby they take place are not fully elucidated: sympathetic activation-mediated mobilization of cells of lymphoid organs, including the spleen, has been suggested. We studied exercise-induced changes (20' of cycloergometer test conducted up to 80% of maximal expected heart rate) in white blood cells (WBC), lymphocyte subsets, plasma catecholamine and cortisol levels in three groups of subjects: swimmers, untrained controls and splenectomized individuals. Physical exercise induced increase of WBC and significant changes in the percentage of most investigated lymphocyte subsets (NK, CD3+, CD4+, CD8+ and CD4/CD8 ratio), except for DR+ cells. No changes occurred in the percentage of CD14+ cells. Norepinephrine (NE) levels increased after effort, while epinephrine (E) and cortisol levels were unchanged. Splenectomized patients displayed similar effort-induced changes in investigated parameters as controls and swimmers. The results support the interactions between physical work and immune response and minimize the role of the spleen in this context.

Adult

Immunological alterations in cluster headache during remission and cluster period. Comparison with low back pain patients.

Cluster headache is a disorder of unknown origin. Some studies have focused their attention on neuroendocrine derangement, others on immunity. To probe central alterations in cluster headache (CH), immune parameters were investigated in cluster headache patients in comparison to low back pain patients and healthy controls. Increases in peripheral blood monocytes found in remission cluster headache patients may be attributable to chronic central nervous system (hypothalamic?) noradrenergic dysfunction or altered beta-endorphin. Alterations in NK+, CD3+ and CD4+ levels found in cluster period cluster headache and low back pain patients are probably pain or stress-related.

Adult

HLA antigens in Italian multiple sclerosis patients.

We analyzed HLA-A, -C, -B, -DR and -DQ specificities in 104 Italian multiple sclerosis patients and in 905 healthy controls. The frequencies of HLA-A23, A26, Cw4, DR3 and, especially DR5 antigens were significantly higher in multiple sclerosis patients than in controls. Patients with progressive course were characterized by high frequencies of B7, B8 and DR3 antigens: Cw1 and DRw11 shows a negative correlation with the extent of intrathecal IgG production. These data confirm that the HLA system may influence the clinical expression and the immune responses to the disease.

HLA Antigens