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Biomedical subjects

G Antonelli

Publications and source records attributed to G Antonelli.

175 records · Page 10Linked to original sources
PubMedDate not supplied

In vivo and in vitro macrophage activation induced by IFN gamma spontaneously released by spleen cells from tumor bearing mice.

Peritoneal macrophages obtained from Lewis Lung carcinoma (3LL) tumor bearing mice release high amounts of soluble factors such as C3,H2O2 and lysosomal enzymes but fail to exert cytotoxic activity on tumor cells. In the present work we show that they acquire this property and become fully activated after in vitro incubation with supernatants derived from cultures of splenocytes from tumor bearing syngeneic mice. The presence of IFN gamma in the above supernatants was detected by immunoblotting analysis and by bioassay. The role played by IFN gamma in macrophage activation was investigated.

Animals↗
PubMedDate not supplied

In vitro inhibition of interferon alpha-2a antiproliferative activity by antibodies developed during treatment for essential thrombocythaemia.

BACKGROUND: Various authors have reported the development of anti-interferon (IFN) antibodies following IFN-alpha treatment for haematological malignancies. So far the methods for detecting these antibodies have not considered the antiproliferative activity of this IFN, which is its most important property in anticancer therapy. METHODS: In this in vitro study we evaluated the ability of anti-IFN alpha-2a neutralising antibodies to inhibit the antiproliferative activity of IFN alpha-2a and lymphoblastoid IFN alpha using megakaryocyte colony growth as the revelatory system. These antibodies were detected in two patients affected by essential thrombocythaemia (ET) who lost their haematological response to IFN alpha-2a, but responded to a subsequent treatment with lymphoblastoid IFN alpha. RESULTS AND CONCLUSION: The results show that the inhibition of megakaryocyte colony growth induced by IFN alpha-2a was totally suppressed in the presence of the two ET patients' sera, whereas the inhibition induced by lymphoblastoid IFN alpha was not significantly affected. These in vitro data demonstrate the high specificity and activity of these antibodies on the antiproliferative effect of IFN alpha-2a.

Adult↗
PubMedDate not supplied

A macrophage derived blastogenic factor -MBF- induces cytokines and cytotoxic effectors in human peripheral blood mononuclear cells.

A soluble macrophage-derived blastogenic factor, previously reported as MBF, is secreted from macrophages activated with galactose oxidase. It was previously shown that MBF is able to induce IFN-gamma production and proliferation of T lymphocytes. In this study we found that MBF is able to induce in human peripheral blood mononuclear cells (PBMC) production of interleukin 1 (IL-1) beta, interleukin 2 (IL-2) and tumor necrosis factor (TNF) alpha and generation of MHC-unrestricted cytotoxic activity. The induction of killer cells is likely to rely on IFN-gamma production in that in PBMC treated with a monoclonal antibody (Mab) against IFN-gamma, the MBF induced cytotoxic activity was drastically reduced. A comparison of MBF induced cytotoxic effectors with those induced by IL-2 showed that both cytotoxic effectors pertain to NK lineage, in that they were CD3- and CD16+. On the contrary, the precursors of MBF and IL-2 induced killer cells were different; MBF cytotoxic precursor cells were highly sensitive to L-Leucine methyl ester (Leu-OME), a drug able to eliminate monocytes and NK cells, whereas IL-2 cytotoxic precursors were unaffected by this drug.

Cell Division↗
PubMedDate not supplied

Relationships between TT virus infection and hepatitis C virus response to interferon therapy in doubly infected patients.

A group of 24 well-characterized patients doubly infected with hepatitis C virus (HCV) and TT virus (TTV) were studied to evaluate whether the loads and number or identity of the genogroups of TTV they carried could affect the response of HCV infection to interferon-alpha (IFN) treatment. The features of HCV infection in the study patients provided a fair representation of the variables that are usually found in considering patients for IFN treatment. The same was true for the features of TTV infection. In particular, plasma loads of TTV varied over a wide range in individual patients, and infection with multiple TTV genogroups was extremely frequent. TTV genogroups 1 and 3 were the most prevalent, followed by genogroups 4 and 5. The HCV response to IFN was evaluated by measuring plasma viraemia at 24 hours and 30 days after initiation of treatment. The results showed that the TTV parameters investigated had little or no impact on the response of HCV to therapy. Due to study design, these results do not exclude that the presence of a concomitant TTV infection can affect how HCV infection responds to treatment. However, they indicate that, should such effects exist, they would be independent on load and genetic features of the infecting TTV.

Adult↗
PubMedDate not supplied

[Exposure to PAHs, urinary 1-pyrenol and DNA adducts in samples from a population living at different distances from a steel plant].

This study aims at measuring association between environmental exposure to PAHs and internal or biologically effective dose biomarkers among 212 individuals living at different distance from the industrial area of Taranto, Italy. Environmental PAH exposure was determined by area monitoring. PAH levels was measured by HPLC UV/FL. Urinary 1-hydroxypyrene levels were measured by HPLC/Fluorescence. The levels of DNA adducts were determined by 32P. post-labelling. A questionnaire was administered to gather personal data, residence, occupational history, alcohol, tobacco smoke, and diet, to control for other sources of exposure to PAH. Blood and urinary samples, drawn from the subjects studied were collected and analysed. A multivariate regression model was used to investigate the influence of several confounding factors. Housing was placed within 1 km from smokestacks in Taranto and Statte, whereas they were more far away in Locorotondo and in Alberobello. The prevalence of current smokers was 31.6%.

DNA Adducts↗
PubMedDate not supplied

Lack of specificity in the mechanisms involved in the enhancement of the concanavalin A driven human T lymphocyte stimulation by beta-endorphin: studies on activation marker expression, cell cycle and interleukin release.

We report on the effects of a physiological concentration of Beta-Endorphin (BE) (10(-12)M) on Concanavalin A (ConA) stimulated human peripheral blood T-lymphocytes and monocytes. We evaluated the effect of timing of BE addition to the culture medium on thymidine uptake, the kinetics of expression of activation markers (CD69, CD25 and CD71) on CD4+ and CD8+ lymphocytes, and of class II MHC antigens on CD14+ cells (monocytes), the kinetics of interleukin-1 (IL-1), interleukin-2 (IL-2) and interferon gamma (IFN-gamma) release, and the cell cycle. Data show that BE is able to influence T lymphocyte only when added together with ConA at the beginning of culture, suggesting its major activity is on the early phases of the T cell response. BE did not increase the amount of class II MHC antigens on monocytes and did not preferentially stimulate CD69, CD25 and CD71 antigen expression on either CD4+ or CD8+ lymphocytes. After 24 hours, the relative proportions of CD4+ and CD8+ lymphocyte in S and G2-M phases were not affected by BE, although the opioid did augment the number of cells in the proliferative compartments of the cell cycle, S and G2-M, indicating an actual increase in the number of cells committed to proliferation. BE did not consistently influence the amount of IL-1, IL-2 and IFN-gamma found in the supernatant of ConA stimulated cultures. The mechanism of the enhancing effect on the proliferative response of normal human lymphocytes to ConA by BE, does not seem to be selective for or unique to specific lymphocyte subsets.

Biomarkers↗
PubMedDate not supplied

Mechanism of production of interferon-gamma: role of arachidonic acid metabolites.

The effects of arachidonic acid metabolites on mitogen-induced interferon (IFN)-gamma production by human peripheral blood mononuclear cells (PBMC) were examined. Both prostaglandins E2 (PGE2) and leukotrienes B4 (LTB4) were produced after macrophage activation stimulated by galactose oxidase (GO) and Staphylococcal enterotoxin B (SEB), two well known inducers of IFN-gamma. To test the involvement of PGE2 and LTB4 in IFN-gamma production, GO- and SEB-activated PBMC were treated with two inhibitors of cyclooxygenase (aspirin and indomethacin) and with an inhibitor of lipoxygenase [nordihydroguaiaretic acid (NDGA)]. The results of these experiments showed that aspirin and indomethacin cause a marked increase of IFN-gamma production by GO- and SEB-activated PBMC. On the contrary, NDGA treatment reduced IFN-gamma production induced by the same agents. Moreover, whereas the addition of exogenous PGE2 reduces IFN gamma production, the addition of exogenous LTB4 does not affect IFN-gamma production. Taken together these findings indicate that arachidonic acid metabolites, produced during mitogenic activation, are involved in the regulation of IFN-gamma production and suggest that, in our system, LTB4 exerts a positive modulating signal while PGE2 represents a negative signal.

5,8,11,14-Eicosatetraynoic Acid↗
PubMedDate not supplied

[Acid-labile alpha interferon produced by peripheral blood mononuclear cells stimulated by cells infected by HIV].

Acquired immunodeficiency syndrome (AIDS) is caused by infection with T-cell tropic retrovirus HIV. The disease is characterized by a profound defect in cell-mediated immunity and a number of serologic abnormalities. Among the serologic abnormalities, the presence of an unusual acid-labile interferon (IFN) has been repeatedly found, and it is considered to be a marker of infection HIV evolving toward illness. Because little is known about the relationships existing between the etiologic agent of AIDS (i.e. HIV) and acid-labile IFN alpha, we approached this problem by testing whether acid-labile IFN alpha is induced in vitro by this virus. In this paper we compared the IFN-inducing activity of free, infectious HIV to that of HIV-infected cells. A number of other enveloped viruses and virus-infected cells were used as controls. Interferon inducing activity by virions as compared to virus-infected cells was determined by incubating human PBMC either with VSV, HSV, and HIV or with cells infected with the same viruses. In this case cells were fixed with glutaraldehyde to prevent virus shedding. While VSV and HSV induced production of acid-stable IFN both as free virions and as virus-infected cells, HIV induced acid-stable IFN when applied as a viral suspension, but it did produce acid-labile IFN when virus-infected cells were used as the inducer. In fact the IFN produced under these circumstances lost more than 80% of its activity when treated to pH2, no matter whether H9/HIV or HIV infected PBMC were used as the inducer. Because acid-lability is a peculiar property of IFN gamma, whereas both native and cloned IFN alpha are completely stable under acid conditions, we compared the IFNs induced by either HIV and HIV-infected cells to standard IFN alpha and gamma preparations with respect to (i) acid stability (ii) neutralization with specific antisera (iii) apparent molecular weight estimated by gel filtration. Results indicate that HIV-induced IFN behaves exactly as standard IFN alpha, as it was completely stable at pH2, totally inactivated by anti-IFN alpha and not by anti-IFN gamma serum, and had apparent molecular weight of 20,000; conversely IFN induced by HIV-infected cells, both H9/HIV and PBMC/HIV, although sharing with IFN alpha both molecular weight and antigenic properties, was inactivated by acid treatment by more than 80%.(ABSTRACT TRUNCATED AT 400 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Generation and characterization of cytotoxic activity against tumor cell lines in human peripheral blood mononuclear cells stimulated "in vitro" by a glucomannan-protein preparation of Candida albicans.

Human peripheral blood mononuclear cells (PBMC) proliferated and generated non-specific cell-mediated cytotoxicity (CMC) after stimulation with a cell-wall glucomannan-protein (GMP) fraction of Candida albicans or chemically-inactivated intact microrganism. No effects were observed using other fungal cell wall components such as glucan or alkali-acid treated glucomannan. The highest CMC level was detected after 7-10 days of PBMC incubation in the presence of 50 micrograms/ml of whole Candida cells and the cytotoxic immunoeffectors elicited by these antigenic stimulations equally affected NK-susceptible (K562) and NK-resistant (Raji, Daudi and Jurkat) tumor cell lines. Both Interleukin-2 (IL-2) and gamma interferon (IFN-gamma) were produced by GMP-stimulated PBMC, the IL-2 peak production constantly preceding that of IFN production. GMP-induced generation of natural CMC was potentiated by the addition of IFN-gamma and a monospecific anti IFN-gamma serum totally abrogated both IFN activity and CMC generation. The cytolytic effectors were shown to be OKT3-, OKT8- and HLA-DR-. They did not possess typical NK markers (e.g. Leu-7 and AB8.28) but were partially recognized by A10, a IgG2a monoclonal antibody reacting to PBMC-NK lymphocytes and activated T cells. These results suggest that the antitumor cytolytic effectors generated in PBMC cultures exposed to Candida material belong either to a discrete subset of natural effectors lacking classical NK markers or to other lymphokine-activated cells. This study also suggests that the human indigenous microrganisms C.albicans may play a role in raising nonspecific antitumor effects in normal host.

Adjuvants, Immunologic↗
PubMedDate not supplied

Resistance to recombinant alpha interferon therapy in idiopathic mixed cryoglobulinemia: reinduction of remission by natural alpha interferon both in antibody-positive and -negative patients.

A subset of patients treated with recombinant interferon alpha-2a (rIFN-alpha 2a) for idiopathic mixed cryoglobulinemia (IMC) developed clinical resistance to therapy after a sustained response. Neutralizing antibodies to rIFN-alpha 2a were found in the sera of three out of four such patients, and in none of the patients who remained responsive to treatment. rIFN-alpha 2a neutralizing antibodies appeared in serum samples of the former three patients 1, 5 and 6 months before evidence for clinical resistance, respectively. Antibody titres to rIFN-alpha 2a were consistently higher than those to natural interferon (nIFN). In the fourth patient with clinical resistance, neutralizing antibodies could not be detected by a very sensitive bioassay in any of several serum samples taken before and after relapse. All the four patients could be reinduced into remission by the administration of nIFN-alpha. These data indicate that mechanisms other than the production of neutralizing antibodies can mediate acquired resistance to IFN therapy. Furthermore, both antibody-related and -unrelated resistance can be overcome by switching to different species of IFN-alpha.

Antibodies↗
PubMedDate not supplied

Antibodies to interferon in patients undergoing IFN therapy: an update.

Interferons (IFNs) are being increasingly used in the treatment of several disorders. Since the early clinical trials, it was documented that some of the patients who received IFN produced antibodies against it. Both neutralizing and nonneutralizing antibodies were detected and it was demonstrated that the development of neutralizing antibodies was often associated with a failure of the IFN therapy. This finding is not actually surprising if one considers that many papers describing natural or therapy-induced development of antibodies to IL-1, IL-2, IL-6, IL-10, G-CSF, GM-CSF, insulin, recombinant factor VIII in man have been published. Since hormones, cytokines, biological modifiers and homeostatic agents are being used for therapeutic applications, the awareness of the possibility that therapy-induced antibodies can develop in man should help define the therapeutic management of many infectious, autoimmune and neoplastic diseases. This paper will review and discuss what is currently known about the technical, biological, and clinical aspects of these "autoantibodies", with particular reference to antibodies to IFN developed during therapy.

Antibodies↗
PubMedDate not supplied

Alteration of thymidine kinase activity in cells treated with an antiviral agent.

A lymphoblastoid cell line, CEM, was rendered resistant to zidovudine (AZT) in vitro by exposure to low but gradually increasing concentrations of the drug. This type of cellular resistance seems to be due to a defect of thymidine kinase (TK) activity that is acquired by cells grown in the presence of AZT. In fact, enzymatic studies with extracts from AZT-resistant cells (CEMazt), have shown that the value of the maximum velocity (Vmax) of TK activity measured with AZT and for deoxythymidine (dThd) is decreased as compared to sensitive CEM cells. Furthermore, the enzyme affinity for AZT and dThd is reduced in CEMazt. Further experiments have shown that such cells do not show resistance to other nucleoside analogs, such as ddI, ddC, AraT and D4T, suggesting that the phosphorylation pathways different from those involving TK are unaltered. Ex vivo experiments performed by using peripheral blood mononuclear cells (PBMC) from HIV infected individuals revealed that a prolonged treatment with AZT may modify the affinity of TK for dThd, thus suggesting that the aforementioned phenomenon may occur also in vivo.

Anti-HIV Agents↗