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Biomedical subjects

W Barcellini

Publications and source records attributed to W Barcellini.

At least 37 records · Page 2Linked to original sources
PubMed1994

Beta-endorphin content in HIV-infected HuT78 cell line and in peripheral lymphocytes from HIV-positive subjects.

We investigated beta-endorphin (BE) content in an HIV-infected cell line and in peripheral blood mononuclear cells (PBM) from HIV-positive subjects. HIV infection increased BE content in HuT78 cell line compared to uninfected cells. Accordingly, BE content was greater in HIV-positive subjects than in healthy controls, both in fresh PBM and in mitogen-stimulated or unstimulated cultured cells. Further, in PHA-stimulated cultures, BE increase was correlated with disease progression. Opioids are known to decrease immune responsiveness in vivo, and it may be that the increased BE concentrations contribute to HIV-associated immune deficiency. In HIV-positive subjects, but not in healthy controls, intracellular BE concentration was positively correlated with PHA-induced PBM proliferation. The latter data suggest an alternative explanation: that the increased BE content represents a paradoxical response of the host in an attempt to balance virus-induced immunodepression. Thus, BE may be important in fine-tuning of the immune response with its up- and downregulation dependent upon differences in immune status.

Adult↗
PubMed1994

TH1 and TH2 cytokine production by peripheral blood mononuclear cells from HIV-infected patients.

OBJECTIVE: To study the TH1-->TH2 cytokine switch, thought to occur during the progression of HIV infection. DESIGN: We investigated interleukin (IL)-2, interferon (IFN)-gamma, IL-4, IL-6 and IL-10 production by phytohaemagglutinin (PHA)-stimulated and unstimulated peripheral blood mononuclear cell (PBMC) cultures from HIV-negative controls and HIV-positive subjects, stratified according to the Centers for Disease Control and Prevention (CDC) criteria. We correlated the above parameters with markers of disease progression. METHODS: Cytokine production was measured in supernatants using enzyme-linked immunosorbent assay (ELISA) in 40 patients and 17 controls. To evaluate disease progression, we also determined CD4+ cell counts, PHA-induced proliferative response, p24 release and spontaneous immunoglobulin (Ig) G and IgM production. RESULTS: In agreement with the TH1-->TH2 switch hypothesis, we found that in the course of HIV disease mitogen-stimulated IL-2 production decreased, spontaneous and stimulated IL-6 production and spontaneous IL-10 secretion increased; IL-4 showed an increasing trend, although it was reduced in HIV-positive subjects. Finally, immunoglobulin production increased over time. In contrast, mitogen-stimulated IFN-gamma and IL-10 production did not change among the CDC categories, although the former decreased and the latter increased in comparison with HIV-negative controls. CONCLUSIONS: Our data partially agree with the TH1-->TH2 switch hypothesis. Since IL-6 and IL-10 are produced by different cell types, whose proportions and functional features vary in the course of the disease, further experiments with purified lymphocyte subsets and monocytes are required. Nevertheless, as already suggested, we believe that a switch from a type 1 to a type 2 response occurs in HIV infection.

Adult↗
PubMed1994

Protection from experimental autoimmune thyroiditis in CBA mice with the novel immunosuppressant deoxyspergualin.

The effects of the novel immunosuppressant Deoxyspergualin (DSP) on the development of experimental autoimmune thyroiditis (EAT) in CBA mice were studied. For EAT induction, the mice were immunized with 100 micrograms of porcine thyroglobulin (p Tg) emulsified in CFA on day 0 and in IFA, for boosting, on day 14. Twenty-eight days after primary immunization, histological and serological signs of EAT occurred in control mice treated with PBS which showed marked lymphoid infiltration of the thyroid glands along with increased serum titres of anti-pTg antibodies. Development of both these EAT features was significantly suppressed when the mice were treated with 2.5 mg/kg body weight DSP, given daily, five times a week, from day -2 to day +28 after immunization. The effect appeared to be dose-dependent and DSP was ineffective when given under the same experimental conditions at the dose of 0.5 mg/kg body weight. No DSP-toxic effects could be observed during the experiment. These results provide further evidence for the powerful immunosuppressive properties of DSP and suggest that this drug may be used in the treatment of autoimmune thyroid diseases and other T-cell mediated autoimmune disorders in humans.

Animals↗
PubMed1994

The effects of thymopentin on the development of SLE-like syndrome in the MRL/lpr-lpr mouse.

Thymopentin (TP-5) is a synthetic pentapeptide that corresponds to the active 32-36 amino acid sequence of the thymic hormone thymopoietin, of which it retains all the immunomodulatory properties. In this study, we have evaluated the effects of long term prophylactic treatment with TP-5 on the clinical, immunological and histological parameters of the SLE-like syndrome that spontaneously occurs in MRL/lpr-lpr (MRL-lpr) mice. TP-5, administered (s.c.) to these mice at the doses of 1, 10 and 100 mg/kg, was given daily, five times a week, from the 9th to the 26th weeks of life. The prophylactic treatment with TP-5 prolonged in a clear dose-dependent fashion the lifespan of MRL-lpr mice as compared with PBS-treated control mice, and the effect reached statistical significance at the doses of 10 and 100 mg/kg. In parallel ex vivo studies, this clinical effect was associated with multiple profound modifications of the immune system including: (i) the reduction of the spontaneous and Con A-induced release of interleukin-4 (IL-4); (ii) the increased secretion of interferon-gamma (IFN-gamma) and IL-6 upon polyclonal mitogenic stimulation, and (iii) the amelioration of the defective Con A-induced lymphoproliferative response. In contrast, although the drug diminished the severity of proteinuria in MRL-lpr mice, it neither reduced histological signs of lupus nephritis nor diminished the serum titres of anti-native DNA and anti-histone autoantibodies. These results indicate that TP-5 displayed powerful immunodulatory activities in a well known model of human SLE.

Amino Acid Sequence↗
PubMed1993

Prevention of cyclophosphamide-induced diabetes in the NOD/WEHI mouse with deoxyspergualin.

Ten out of 20 (50%) 17-week-old female NOD/WEHI mice developed an acute form of autoimmune diabetes when injected with two large doses of cyclophosphamide (CY), given at 14-day intervals. If these mice were treated under a prophylactic regimen with 2.5 mg/kg body weight per day of the novel immunosuppressant deoxyspergualin (DSP) the onset of diabetes was completely prevented. Moreover, DSP-treated animals showed reduced signs of pancreatic insulitis, had lower percentages of splenic lymphoid cells (SLC) expressing IL-2 receptors and Ly-6C antigens on their surfaces, and these cells released lower amounts of interferon-gamma (IFN) when stimulated in vitro. These data, providing evidence for the capacity of DSP to protect NOD/WEHI mice from experimental autoimmune diabetes and to modulate histo-immunological pathogenic pathways, indicate DSP as a drug of potential interest in the treatment of human insulin-dependent diabetes mellitus.

Animals↗
PubMed1993

Autoantibodies against beta 2-microglobulin-free HLA antigens in AIDS patients.

Serum samples from 88 human immunodeficiency virus (HIV)-positive drug addicts have been investigated for the presence of antibodies to both beta 2-microglobulin (beta 2m)-free and beta 2m-associated HLA class I molecules. Using HIV-negative drug addicts as background control, we found that none of the Centers for Disease Control (CDC) stage II, 9.1% of CDC III, 36.4% of CDC IV A, and 45.5% of CDC IV C1 patients had significant levels of autoantibodies competing with the binding of the monoclonal antibody specific for beta 2m-free HLA I (L31 mAb). Using the mAb 01.65, recognizing the beta 2m-associated form of HLA class I molecules, a similar percentage of positive samples was found in the CDC II, CDC III, and CDC IV A patient groups; conversely, the percentage of positive serum samples was lower in the CDC IV C1 group. A lower number of systemic lupus erythematosus serum samples and none of the specimens from healthy adult subjects or patients suffering from recurrent Epstein-Barr virus infections were positive in both assays. Our data demonstrate the existence of an ongoing HLA class I-specific autoimmune response during AIDS disease development, which probably reflects a molecular mimicry between autologous histocompatibility antigens and HIV components. The relationship between the prevalence of autoantibodies against beta 2m-free HLA class I and disease progression suggests a possible pathogenetic role of these antibodies in the induction of the HIV-associated immune deficiency.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Immunopharmacological activity of cefodizime in young and elderly subjects: in vitro and ex vivo studies.

The biological response modifying activities of cefodizime (CDZ), a new third-generation cephalosporin, were investigated in vitro and ex vivo. In vitro investigations using cells isolated from the blood of young healthy donors showed no stimulating activity of CDZ on peripheral blood lymphocytes, natural killer cell activity, IL-1 production by adherent mononuclear cells, PMN chemiluminescence or PMN chemotaxis. A slight but statistically insignificant increase in PMN phagocytosis and phagocytic index was observed in the same population. IL-1 production was increased in three subjects with low resting state values. In a controlled ex vivo study, 20 healthy elderly subjects selected on the basis of depressed phagocytic function were treated with CDZ 1 g i.m. b.i.d. or placebo for eight days. PMN function was determined at baseline and on the day after the last dose. In the CDZ group a significant increase in both phagocytosis and phagocytic index was found, while there were no changes in the placebo group. In conclusion, CDZ restored depressed PMN phagocytic function in a population of elderly subjects. Patients with impaired PMN function who require antibiotic treatment may benefit from this activity of CDZ.

Adult↗
PubMed1992

Antibodies to endothelial cells in primary vasculitides mediate in vitro endothelial cytotoxicity in the presence of normal peripheral blood mononuclear cells.

Twenty-eight out of 62 patients with Wegener's granulomatosis and micropolyarteritis display circulating antiendothelial cell antibodies (AECA) detectable by a cell surface radioimmunoassay. These antibodies do not induce an in vitro endothelial damage either alone or in the presence of fresh complement; however, 50% of IgG-AECA positive sera can be cytotoxic in the presence of human normal peripheral blood mononuclear cells (PBM) at high effector/target ratios. The specificity of the PBM-mediated cytotoxicity is supported by the absence of the phenomenon in AECA negative sera, by the disappearance of the lytic effect after absorption of AECA, and by the finding that cellular-mediated cytotoxicity can be reproduced by purified IgG-AECA positive fractions. On the contrary, polymorphonuclear leukocytes or adherent mononuclear cells are not involved in such a cytotoxic activity. AECA seem to be directed against determinants consitutively expressed on the endothelial surface since the activation of endothelial cells by interleukin-1 beta or interferon-gamma affects neither the antibody binding nor their ability to mediate 51Cr release in the presence of PBM. These findings favor the hypothesis for a possible direct pathogenetic role of circulating AECA in the in vivo vascular damage.

Adult↗
PubMed1992

Enrichment of IgG anti-DNA-producing lymphoblastoid cell lines by antigen-coated immunomagnetic beads.

In this paper we describe the establishment of four anti-DNA-producing lymphoblastoid cell lines (LCL) by Epstein-Barr virus (EBV) infection of peripheral blood B-cells from a patient with systemic lupus erythematosus. The LCL showed a heterogeneous cell composition: the frequencies of cells in active proliferation, cells secreting IgG or IgM, and cells effectively producing IgG or IgM anti-DNA were estimated by limiting dilution analysis. The cells producing anti-DNA antibodies were a small fraction of the whole cell population constituting the LCL. In order to enrich the fraction of cells producing the desired antibody we performed a positive selection by DNA-coated immunomagnetic beads. Results show that in two out of three IgG anti-DNA-secreting LCL the frequency of DNA-producing cells increased after incubation with DNA-coated beads. At variance, IgM anti-DNA-secreting cells were completely lost after immunomagnetic separation. This approach could represent a further tool to obtain better fusion partners to construct stable hybrids secreting human monoclonal antibodies. The advantages of the presented technique would be: (a) removing of the fraction of low-affinity IgM-producing cells, which is often prevalent in EBV-induced LCL; and (b) the enrichment of IgG anti-DNA producing cells, which better represent the antibodies involved in the pathogenesis of the disease.

Adult↗
PubMed1992

In vitro and ex vivo effect of tiaprofenic acid on human peripheral blood mononuclear cells.

The effect of the non-steroidal anti-inflammatory drug (NSAID) tiaprofenic acid on different human immune parameters was investigated in vitro or following in vivo administration in healthy adult volunteers. Results from the in vitro study demonstrated an increased mitogen-induced blastogenesis and interleukin 2 (IL-2) production together with a reduced polyclonal immunoglobulin (Ig) secretion in the presence of the drug. Results from the ex vivo study showed that treatment with tiaprofenic acid had no significant effects on the immune parameters investigated, i.e. unstimulated and mitogen-induced proliferation and IL-2 production, spontaneous and stimulated Ig synthesis, lymphocyte subpopulations, serum Ig and complement levels.

Adult↗
PubMed1992

The effects of deoxyspergualin on the development of diabetes in diabetes-prone BB rats.

The effects of the administration of the recently discovered immunosuppressant 15-Deoxyspergualin (DSP) on the development of insulin-dependent diabetes mellitus (IDDM) in diabetes-prone BB rats were studied. The data show that 2 mg/kg body weight DSP, administered six times a week from the 30th day up to the 105th day of age, significantly reduced the incidence of diabetes in diabetes-prone BB rats as compared with the PBS-injected controls. The drug was also able to reduce the signs of pancreatic insulitis and the percentages of W3/25+ and OX6+ splenocytes. Interruption of the treatment resulted in a later onset of diabetes in a high percentage of animals within 41 days. These findings suggest that 15-DSP may temporarily reverse the pathogenic mechanisms leading to beta cell destruction and autoimmune diabetes in a well-known experimental model of human insulin-dependent diabetes mellitus.

Animals↗
PubMed1991

FK-506 prevents diabetes in diabetes-prone BB/Wor rats.

The effect of the immunosuppressant FK-506 on the development of diabetes in BB/Wor rats was investigated. Using a treatment schedule (25 micrograms i.m. from day 27 to 120), not associated with detectable general ill effects, this drug was found to completely inhibit the appearance hyperglycemia and to reduce the histological signs of pancreatic insulitis. The treatment was also able to reduce the percentages of Ia+ T-lymphocytes and to block the appearance of detectable serum levels of gamma interferon (IFN).

Animals↗
PubMed1990

Correlation between islet cell antibodies and anti-cytomegalovirus IgM and IgG antibodies in healthy first-degree relatives of type 1 (insulin-dependent) diabetic patients.

To investigate whether cytomegalovirus (CMV) infection may be related to islet cell antibodies (ICA) production and/or to insulin-dependent diabetes mellitus (IDDM) development, we have analyzed the prevalence of anti-CMV, IgM, and IgG antibodies and of ICA in 80 healthy siblings of IDDM patients (HSIDDP) and in 60 control subjects with negative familiar anamnesis of IDDM. HSIDDP and controls were also typed for HLA-A-B-C and DR antigens. IgM and IgG anti-CMV were detected by an ELISA method, whereas the ICA assay was performed by standard indirect immunofluorescence on 5-microns unfixed sections of human pancreas. HLA-A-B and C antigens were studied by standard microlymphocytotoxicity; DR antigens were also studied by a standard microlymphocytotoxicity on a B-enriched lymphocyte population. Our results indicate a significant association (P less than 0.0001) between high titers of anti-CMV IgG antibodies and ICA in HSDIDDP, whereas no correlation was found between the presence of any HLA-A-B-C and DR antigens and the prevalence of anti-CMV IgM and IgG antibodies and/or ICA. Thus, these data may support the hypothesis that a chronic CMV infection may be associated with ICA production whereas other factors seem to be needed for the complete development of type 1 diabetes.

Adolescent↗