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Biomedical subjects

G Antonelli

Publications and source records attributed to G Antonelli.

At least 109 records · Page 6Linked to original sources
PubMed1990

The biological basis for clinical use of interferon.

Interferons represent the body's most rapid defence against virus infection. Natural recovery from viral infections is correlated with interferon production; the inhibition of interferon enhances the severity of infection and interferon has been shown to protect animals from some viral infections. beta-Interferon is produced by fibroblasts in response to viral infection. Leucocyte (a) interferon may be induced by foreign or infected cells or by viruses, and it is continuously released into the bloodstream during infection, declining with time. gamma-Interferon are produced later in viral infection by virus-sensitized T lymphocytes. The antiviral action of interferon is induced by interaction with specific receptors on cell surfaces leading to translation of antiviral proteins. Interferons may also enhance immune responses by increasing expression of lymphocyte surface antigens and by increasing the cytotoxic activity of natural killer cells. In chronic hepatitis B and C, it seems likely that interferon's antiviral activity is responsible for the early fall of viral products, while its immunomodulatory activity is responsible for long-term effects, including the destruction of infected hepatocytes, with persistent loss of viral antigens and seroconversion.

Hepatitis, Viral, Human↗
PubMed1990

Polymorphic effects of exogenous gangliosides on antigen-induced lymphoproliferation and generation of MHC unrestricted cell mediated cytotoxicity.

Cell membrane gangliosides have been shown to be involved in a number of biological processes including cell adhesion, signal transduction and ligand receptor interactions. In this paper we analyzed the effects of a mixture of bovine brain gangliosides, currently in clinical use, on cell mediated immune responses in vitro. We show here that exogenous gangliosides inhibit mitogen and alloantigen induced lymphoproliferation. On the other hand effects on antigen induced blastogenesis were exquisitely dose dependent in that while high doses of gangliosides inhibited lymphoproliferation, probably by interfering in interleukin 2 receptor interactions, lower doses significantly enhanced antigen induced responsiveness. We also report that gangliosides inhibit the generation of lymphokine activated killer cells. Altogether, these data underline the immunoregulatory potential and the polymorphism of effects of exogenous gangliosides.

Cytotoxicity, Immunologic↗
PubMed1990

Increased autoreactive T cell frequency in tuberculous patients.

The development of putative self-MHC-reactive T cells and their precursor frequency was estimated in peripheral blood lymphocyte cultures stimulated in vitro with PPD. The role of foreign antigen in the generation of self-MHC-reactive T cells in vivo was analyzed by comparing the frequency of autoreactive T cells in the peripheral blood of tuberculous patients with that observed in healthy individuals. It was found that PPD in vitro and Mycobacterium tuberculosis infection in vivo increased substantially the generation of autoreactive T cells. Autoreactive T cell clones were shown (1) to recognize self MHC class II products; (2) to release gamma interferon in the absence of exogenous antigen, and (3) to express autocytotoxic activity. All these findings suggest that self-MHC-reactive T cells may be involved in the inflammatory response to M. tuberculosis.

Cells, Cultured↗
PubMed1990

Biological activity of gamma interferon.

Gamma interferon (IFN) is mainly produced, under natural conditions, by antigen-specific T lymphocytes during the immune response. Cooperation with macrophages is required. Although discovered in 1965 as an antiviral agents, today this type of IFN is considered a lymphokine deeply involved in the regulation of several immunological reactions such as: cytotoxicity; expression of surface antigens, mainly MHC antigens; cellular differentiation; antibody production; macrophage activation. In this review the authors discuss some aspects of the biology of gamma IFN as pleiotropic lymphokine as well as the cellular events leading to gamma IFN production.

Animals↗
PubMed1989

Comparative study on the antiviral activity of tumor necrosis factor (TNF)-alpha, lymphotoxin/TNF-beta, and IL-1 in WISH cells.

We find that pretreatment of WISH cells with tumor necrosis factor (TNF)-alpha, IL-1, and lymphotoxin/TNF-beta is capable of inducing an antiviral state in these cells, thereby protecting them from vesicular stomatitis virus cytopathic effect. Furthermore, we find that such a treatment causes a major inhibition of the synthesis of VSV proteins, as analyzed by SDS-PAGE. The 2-5A synthetase activity is also increased by treating the cells with doses of cytokines effective in antiviral protection. In this cell system, inclusion of polyclonal antibodies to IFN-beta during cytokine pretreatment abrogates the antiviral state elicited by the above cytokines, while antibodies to IFN-beta 2/IL-6 fail to abolish the cytokine-induced antiviral effects.

2',5'-Oligoadenylate Synthetase↗
PubMed1989

The in vitro antiviral activity of tumor necrosis factor (TNF) in WISH cells is mediated by IFN-beta induction.

We present evidence showing that TNF is capable of inducing an antiviral state in WISH cells thereby protecting them from the cytopathic effect of vesicular stomatitis virus. Establishment of the antiviral state requires pretreatment with TNF. Such pretreatment not only protects the cells in a dose-dependent manner, but it markedly reduces virus yield as well. Kinetic studies have shown that a pretreatment period as short as 4 h at 37 degrees C is effective in conferring protection. The antiviral activity of TNF could be attributed to the induction of IFN-beta. In fact, polyclonal antibodies to IFN-beta completely neutralized the antiviral state elicited by TNF. 2-5A synthetase activity was significantly enhanced when the cells were treated with doses of TNF that afforded antiviral protection. Finally, addition of specific antibodies to IFN-beta 2 (IL-6) during TNF pretreatment failed to abolish the antiviral state, thus suggesting that IFN-beta 2 is not involved in the TNF-induced antiviral state. Also, a homogeneous IFN-beta 2 preparation failed to exert antiviral activity in our cell system.

2',5'-Oligoadenylate Synthetase↗
PubMed1989

Interleukin-2, interleukin-2 receptor and gamma-interferon synthesis by peripheral blood mononuclear cells in chronic hepatitis delta virus infection.

The behaviour of the immune system during liver damage caused by chronic hepatitis delta virus (HDV) infection was evaluated by assessing, in 16 patients with HBsAg+ chronic liver disease and HDV superinfection (15 HBeAg-, 1 HBeAg+), phytohaemagglutinin (PHA)-induced interleukin-2 synthesis and interleukin-2 receptor expression, PHA and staphylococcal enterotoxin B (SEB)-induced gamma-interferon synthesis and, in some cases, the presence of hepatitis B virus DNA (HBV-DNA) within peripheral blood mononuclear cells (PBMC). The results were compared to those obtained in 13 patients without HBV replication (i.e., serum HBV-DNA and liver HBcAg-negative), in 15 with HBV replication (i.e., serum HBV-DNA and/or liver HBcAg-positive) with chronic liver disease without HDV superinfection, and in 15 HBsAg-negative healthy control subjects. The lymphokine pattern in HDV infection was comparable to that of healthy subjects and of HBV non-replicating patients without HDV superinfection. Interleukin-2 receptor expression and gamma-interferon synthesis were however significantly decreased in HDV-negative patients with active HBV replication. HBV-DNA was detected in PBMC from 8 of 23 patients, without any correlation with the lymphokine pattern. Our results suggest that in HDV-related chronic liver disease, immune system alterations are unlikely. HDV superinfection does not affect the occurrence of HBV-DNA sequences within the leukocytes. HBV-DNA in PBMC does not interfere with the interleukin-2 system nor with the gamma-interferon response in HBV- and HDV-related chronic liver disease.

Adult↗
PubMed1989

Low incidence of neutralizing antibody formation to interferon-alpha 2b in human recipients.

Patients receiving large amounts of interferon (IFN), particularly cloned IFN-alpha, have been reported to develop antibodies to IFN-alpha. We used a neutralization technique bioassay to monitor 175 patients undergoing recombinant (r) IFN-alpha 2b therapy in an attempt to correlate antibody production to disease progression. Only 1 patient being treated for chronic myelogenic leukemia produced antibodies. Our findings indicate that rIFN-alpha 2b has minimal antigenicity, even when administered for prolonged periods of time.

Adolescent↗
PubMed1989

Pathogenetic aspects of uremic cardiomyopathy.

We have considered just some of the many factors which may affect myocardial function, assessed by means of echocardiography, in uremic patients. Our findings support the view of a multifactorial genesis of the cardiac involvement in uremic patients.

Adult↗
PubMed1988

Cell-mediated cytotoxicity in glioma-bearing patients: differential responses of peripheral blood mononuclear cells to stimulation with interleukin-2 and microbial antigen.

Peripheral blood mononuclear cells (PBMC) of malignant glioma-bearing patients were stimulated in vitro with Interleukin-2 (IL-2) or a glucomannan-protein antigen of Candida albicans (GMP) then assayed for proliferation, production of IFN-gamma, and generation of cytotoxic effectors against either K562 tumor cell line or freshly-cultured allogenic glioma cells. PBMC of healthy, age and sex-matched subjects were the controls. PBMC of glioma-bearing patients did not differ, as a whole, from PBMC of healthy donors in IL-2 or GMP-induced proliferation. However, they showed a lesser ability to produce IFN as well as a substantial inability to generate cytotoxic effectors following GMP stimulation. PBMC of glioma patients were fully responsive to IL-2 in cytotoxicity generation, as were the PBMC from normal subjects. The results suggest that glioma patients may have a defective antigen-mediated activation of natural cytotoxic effectors. This hyporesponsiveness is not accompanied by depressed lymphoproliferation and does not apparently involve a reduced response to IL-2.

Adult↗
PubMed1988

A macrophage-derived factor different from interleukin 1 and able to induce interferon-gamma and lymphoproliferation in resting T lymphocytes.

A novel monokine different from interleukin 1 (IL-1) is secreted from human or murine macrophages stimulated with galactose oxidase, a well-characterized enzyme able to induce marked polyclonal activation of lymphocytes. This monokine, preliminarly termed macrophage-derived blastogenic factor (MBF), stimulates resting T lymphocytes to produce interferon (IFN)-gamma and to proliferate. The apparent MW of MBF ranges between 29,000 and 35,000, although some active fractions show smaller MW ranging from 2000 to 7000, as demonstrated by gel filtration. The biological relationship between MBF and IL-1 was examined and it was found that MBF (1) is able to induce IFN-gamma production and proliferation by T lymphocytes in the absence of other inducers, (2) is not able to activate PHA-stimulated C3H mouse thymocytes, (3) is not able to induce production of IFN-beta by fibroblast cultures, (4) is resistant to proteolytic enzymes, and (5) is not neutralized by antibodies to IL-1. MBF was released in the macrophage supernatants in two waves after the oxidation process, namely, after 15 min and 2.5 hr, and each wave was capable of inducing lymphocyte activation at dilutions up to 1:32. Because the oxidation of galactose residues on cell surface structures is considered a general feature of lymphocyte activation whatever the inducer, it seems that MBF may be a mediator involved in mitogenic activation of T cells leading to IFN-gamma production and proliferation.

Animals↗
PubMed1988

Mechanism of human interferon-gamma production: involvement of beta-2-microglobulin.

The ability of several monoclonal antibodies (MoAbs) against beta-2-microglobulin (beta 2m) to inhibit interferon-gamma (IFN) production was assayed in peripheral blood mononuclear cells (PBMC). All of them strongly reduce IFN-gamma induction by galactose oxidase (GO), a well-characterized enzyme capable of activating T lymphocytes through mediation of macrophages. In contrast, many MoAbs directed against HLA class I (heavy chain) and class II antigens do not inhibit IFN induction by GO. On the other hand, anti-beta 2m MoAbs do not effectively reduce IFN-gamma induction by A23187, a calcium ionophore that acts on T cells in the absence of accessory cells. Competition experiments demonstrate that (i) the inhibition of anti-beta 2m antibodies was specific for beta 2m protein, and (ii) beta 2m is not itself the site of action of GO. Moreover, it is demonstrated that the addition of beta 2m to oxidated PBMC strongly enhances subsequent IFN-gamma production. Oxidation of galactose residues on glycoproteins of macrophage membrane is an obligate step for IFN-gamma induction whatever the inducer, thus our results suggest that beta 2m is involved in the mechanism of induction of IFN-gamma.

Antibodies, Monoclonal↗
PubMed1988

Early steps in interferon-gamma production: possible involvement of Ca2+-calmodulin-dependent enzymes.

A23187 in combination with phorbol myristate acetate (PMA) strongly induces production of interferon-gamma (IFN-gamma) by human peripheral blood mononuclear cells (PBMC) and even by murine PBMC, which respond poorly to A23187 alone. Macrophage depletion of PBMC strongly reduces IFN-gamma production induced by several mitogens, but does not affect IFN-gamma production induced by A23187 and PMA. In addition the same stimuli are able in combination to induce strong amounts of IFN-gamma, even in the Jurkat T cell line. The protein kinase C inhibitor 1-(5-isoquinolinylsulfonyl)-2-methyl-piperazine (H-7) and the calmodulin antagonist N-(6-aminoehexyl)-5-chloro-1-naphthalenesulfonamide (W-7) were examined for their ability to inhibit IFN-gamma production induced by PMA and A23187. At concentrations near the Ki for protein kinase C, H-7 failed to inhibit PMA- and A23187-induced IFN-gamma production. In contrast, W-7 at low concentrations inhibited IFN-gamma production induced by the same stimuli. In addition OAG, which is known to directly activate protein kinase C, failed to act synergistically with A23187 in the induction of IFN-gamma. On the basis of these results we propose that A23187 and PMA may mimic the early steps of lymphocyte activation, without the requirement of macrophage, bypassing antigen-, or lectin-induced signal. Our results suggest that Ca2+-calmodulin-dependent reactions other than protein kinase C activation may be essential for IFN-gamma production, at least at level of the producing cells.

Animals↗