Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001175 (AIDS)
 120,706 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The tolerance and toxicity of interferon-gamma (IFN-gamma) was assessed in a phase I/II study of 21 patients with acquired immune deficiency syndrome (AIDS). A highly purified preparation of human recombinant E. coli-produced IFN-gamma was given i.v. twice weekly for an 8 week period. Patients were enrolled in the study in groups of four or five; the initial group received an IFN-gamma dose of 0.03 mg/m2 and subsequent groups received higher IFN-gamma doses of 0.3, 1, or 3 mg/m2. Toxicity resulting from IFN-gamma was minimal and the therapy was well tolerated even at the maximum dose (3 mg/m2). No patients developed antibodies that neutralized IFN-gamma. Clinical responses were observed in 3 of 17 patients with Kaposi's sarcoma (KS). A complete clinical response was achieved in one individual and a partial, temporary regression of KS lesions was observed in two other patients. HIV p24 antigen was decreased in plasma samples obtained from six of nine patients with initially detectable HIV protein. These data suggest that IFN-gamma should be considered as a therapeutic agent, possibly with other antivirals, in the treatment of patients with AIDS.
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PMID:Use of IFN-gamma in patients with AIDS. 167 12

Organisms belonging to the Mycobacterium avium complex (MAC) are associated with life-threatening bacteremia in patients with the acquired immunodeficiency syndrome (AIDS). As these organisms survive within macrophages, we examined the ability of recombinant human granulocyte-monocyte colony-stimulating factor (GM-CSF) to activate human monocyte-derived macrophages to inhibit the intracellular growth or kill the most mouse-virulent MAC strain in our collection that belongs to serotype 1. While unstimulated cells did not inhibit intracellular growth of MAC, macrophages activated by GM-CSF (10-10(4) U/ml) inhibited or killed up to 58 +/- 5% of the initial inoculum. This activation was dose-dependent, with maximal change occurring with a dose of 100 U/ml after 72 hr exposure. Inhibition or killing was demonstrated if GM-CSF was given both before or after establishment of infection. The combination of GM-CSF (10(2) U/ml) plus TNF (10(2) U/ml) augmented macrophage killing (range, 31 +/- 4%) compared with GM-CSF (10(2) U/ml) alone, but the combination of recombinant human interferon-gamma (IFN gamma) plus GM-CSF resulted in a significant decrease in intracellular inhibition of growth or killing (13.3 +/- 2%) compared with 57.7 +/- 5% obtained with GM-CSF alone. These results indicate that: 1) GM-CSF can activate macrophages to inhibit intracellular growth or kill MAC; 2) killing may be augmented by TNF; and 3) IFN gamma may impair GM-CSF-dependent macrophage activation.
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PMID:Recombinant granulocyte-macrophage colony-stimulating factor activates human macrophages to inhibit growth or kill Mycobacterium avium complex. 211 63

AS101, a synthetic organotellurium compound, was found to have immunomodulating properties by initiation of cytokine production in vitro and in vivo. Phase I/II clinical trials currently in progress on AIDS and cancer patients treated with AS101 show significant increases in various immunological parameters, with minimal toxicity. Recently, AS101 and the protein kinase C (PKC) inducer, phorbol myristate acetate (PMA), were shown to synergize in the secretion of interleukin-2 (IL-2) and colony-stimulating factor (CSF) in vitro, by human and mouse lymphoid cells. The bryostatins, a group of natural macrocyclic lactones isolated from marine invertebrates (Bugula neritina) have been reported to be potent PKC activators with no tumour promoting activity. In this study, we investigated the synergistic effect of AS101 and a partially purified preparation of bryostatin on the production of several cytokines. Our data confirm the presence of synergism, which greatly enhances cell proliferation, IL-2, tumour necrosis factor (TNF) and interferon-gamma (IFN-gamma) secretion by human mononuclear cells (MNC) and the production of IL-2 and TNF by mouse cells. The absence of tumour-promoting activity of the bryostatins makes them particularly good candidates, in combination with AS101, for immunomodulation in vivo in clinically immunosuppressed conditions.
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PMID:Cytokine secretion effected by synergism of the immunomodulator AS101 and the protein kinase C inducer bryostatin. 211 79

The expression of HLA class II glycoproteins by monocytes from HIV-infected individuals was evaluated. We found no differences in HLA-DR, HLA-DQ, or HLA-DP expression by freshly isolated monocytes from patients with clinical AIDS, HIV-infected patients without AIDS or from uninfected individuals. However, monocytes from HIV-infected individuals without AIDS responded better to stimulation with recombinant human interferon-gamma (IFN-gamma) than did monocytes from patients with clinical AIDS or from uninfected individuals. The response to IFN-gamma stimulation by monocytes from patients with clinical AIDS was different. Thus, the largest increases in the percentage of cells expressing HLA-DR was associated with the smallest changes in the fluorescence intensity of the population that is observed following stimulation of monocytes from other patient populations.
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PMID:HLA class II glycoprotein expression by monocytes from HIV-infected individuals: differences in response to interferon-gamma. 212 60

Lymphocytes expressing interferon-gamma (IFN-gamma) on their surface were evaluated in 61 patients, all IV drug abusers, infected with human immunodeficiency virus type 1 (HIV-1), and in 85 healthy subjects (61 of whom were blood donors and 24 HIV-1 seronegative IV drug abusers). Data obtained demonstrated that IFN-gamma-expressing T lymphocytes, mostly CD8+ cells, were present in HIV-1-infected patients, and that their percentage, always higher in HIV-1-infected patients than in healthy subjects (p less than or equal to 0.001), increased with progressive stages of HIV-1 infection. At the same time other markers of T-cell activation, namely interleukin-2 receptor (rIL-2), transferrin receptor, and HLA-DR were also found to be positive in some of the HIV-1-infected subjects. The presence in the HIV-1-infected patients of activated CD8+ T cells, which are resistant to HIV-1 infection, may suggest that these cells are able to respond to continuous and progressive viral expression (HIV or/and other viruses) and may be a component of the specific response to HIV-1.
AIDS Res Hum Retroviruses 1990 Jul
PMID:Interferon-gamma marks activated T lymphocytes in AIDS patients. 214 13

Interferon-gamma-induced protein 10 is a 10-kd protein produced by human keratinocytes following an exposure to interferon gamma. Keratinocytes within psoriatic plaques and within delayed-type hypersensitivity reactions have been shown to stain strongly with an affinity-purified rabbit antibody prepared against interferon-gamma-induced protein 10, suggesting a possible role for interferon gamma in the production of the lesions. A psoriasiform eruption has been seen in patients with acquired immunodeficiency syndrome (AIDS). Its severity appears to correlate with the degree of immunodeficiency in the early stages of AIDS. We stained 10 lesions of psoriasiform dermatitis of AIDS with the anti-interferon-gamma-induced protein 10 antibody using immunoperoxidase techniques. As controls, we studied 10 lesions of non-AIDS psoriasis, six lesions of seborrheic dermatitis with psoriasiform hyperplasia, one lesion of lichen simplex chronicus, and four biopsy specimens of normal skin from patients with AIDS. In addition, normal skin specimens taken from patients with AIDS and human immunodeficiency virus-negative patients at time of autopsy were examined. An identical, strong and diffuse staining pattern was seen in all cases of psoriasiform dermatitis of AIDS, non-AIDS psoriasis, seborrheic dermatitis, and lichen simplex chronicus. The specimens of normal skin showed only weak basal layer staining with anti-interferon-gamma-induced protein 10. Thus, the presence of interferon-gamma-induced protein 10 in keratinocytes was associated with psoriasiform hyperplasia and could be detected in both AIDS-associated and classic psoriasis.
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PMID:Detection of the interferon-gamma-induced protein 10 in psoriasiform dermatitis of acquired immunodeficiency syndrome. 214 26

Mycobacterium avium is a cause of disseminated infection in AIDS patients. The pathogenicity of M. avium for human monocytes was examined in an in vitro model. Peripheral blood monocytes obtained from 13 healthy donors were precultured for 2 days before infection. Monocytes were infected with six AIDS-associated and three non-AIDS-associated strains and four strains of M. avium selected on the basis of colonial morphology. Uptake of M. avium detected by counting intracellular acid-fast bacilli differed according to colonial morphology: Bacteria with round and opaque colony forms were phagocytosed more readily than those with flat colonies. Virulence as defined by intracellular growth was also partly associated with colonial morphology. Some but not all bacilli with flat colony forms multiplied in human monocytes; strains of the round opaque colonial form did not. The effects of recombinant human interferon-gamma on M. avium infection also were examined. Pretreatment of monocytes suppressed phagocytosis. After infection, coculturing usually augmented mycobacterial growth inhibition by human monocytes, but these effects were variable from strain to strain. Overall, interferon-gamma produced a small but statistically significant inhibition of intracellular growth in three of four strains tested.
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PMID:Strain- and donor-related differences in the interaction of Mycobacterium avium with human monocytes and its modulation by interferon-gamma. 215 42

The study of monocyte/macrophage functions after human immunodeficiency virus type 1 (HIV-1) infection may help in understanding the pathogenesis of AIDS. The production of four cytokines, tumor necrosis factor alpha (TNF alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and granulocyte-macrophage colony-stimulating factor (GM-CSF), by peripheral blood monocytes/macrophages was evaluated after in vitro infection with HIV-1. HIV-1 infection of these monocytes/macrophages did not result in release of any of these cytokines. Similarly, treatment of uninfected cells with purified recombinant HIV-1 envelope protein did not result in cytokine production. After stimulation with endotoxin or endotoxin plus interferon-gamma, HIV-1-infected monocytes/macrophages produced amounts of TNF alpha, IL-6, GM-CSF, and IL-1 beta comparable to that of uninfected cells. HIV-1 infection does not appear to induce or alter cytokine production by mononuclear phagocytes, which retain the capacity to produce these cytokines after endotoxin stimulation.
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PMID:Production of cytokines by peripheral blood monocytes/macrophages infected with human immunodeficiency virus type 1 (HIV-1). 218 29

The protective immune response to human immunodeficiency virus type 1 (HIV-1) induced by vaccination will likely include cellular immune responses. We measured lymphoproliferative responses in persons vaccinated with a baculovirus-derived recombinant gp160 candidate AIDS vaccine. Twelve volunteers received either 40 micrograms of rgp160, 80 micrograms of rgp160, hepatitis B vaccine, or alum adjuvant alone on days 0, 30, and 180. Peripheral blood lymphocytes were collected on days 0, 28, 60, 120, 210, and 270 and were cryopreserved. Lymphocyte proliferation to mitogens and rgp160 with and without interleukin-2 stimulation were determined, and lymphokine production and antibody synthesis were measured. All vaccinees responded normally to stimulation with phytohemagglutinin and concanavalin A. One of 3 vaccinees who received 40 micrograms of rgp160, 2 of 2 vaccinees who received 80 micrograms of rgp160, and no controls developed rgp160-specific lymphoproliferative responses. No differences in the production of lymphokines (interleukin-2 and interferon-gamma) after stimulation with mitogens or rgp160 were found when rgp160 vaccinees and controls were compared. We conclude that rgp160 candidate vaccine induces antigen-specific lymphoproliferative responses in humans and does not interfere with immunocompetence as measured by in vitro responses to mitogen stimulation.
AIDS Res Hum Retroviruses 1990 Apr
PMID:Lymphoproliferative responses to mitogens and HIV-1 envelope glycoprotein among volunteers vaccinated with recombinant gp160. 218 3

Peripheral blood monocytes from human immunodeficiency virus (HIV)-infected individuals or AIDS-related complex/AIDS patients ex vivo exhibit distinct alterations in some but not all immune functions. In studies presented here, monocytes from healthy donors were infected with HIV 1 in vitro and co-cultures with autologous uninfected T lymphocytes were set up. The monocyte/macrophage (M phi)-dependent T cell function was determined by measurement of proliferative and secretory [interleukin (IL)2, interferon-gamma] responses to lectin (phytohemagglutinin), mitogen (anti-CD3 monoclonal antibody), or recall antigen (tetanus toxoid, tuberculin). Accessory function of M phi was normal after HIV infection when optimal amounts (10%-20%) were added to the T lymphocytes. However, HIV infection of M phi significantly decreased T cell proliferative responses and secretion of IL2 when supplemented at limited dilution (0.5%-5%), although interferon-gamma production was not affected. Whereas the lipopolysaccharide-triggered M phi production of IL1 was not impaired by HIV 1 infection, there was a significant decrease in this response when anti-CD3 monoclonal antibody or tetanus toxoid were used to trigger the peripheral blood mononuclear cells. The impairment of proliferation of T lymphocytes in the presence of HIV 1-infected M phi could be overcome by addition of exogenous IL 1. Taken together, these data clearly show that the mononuclear phagocyte-dependent enhancement of stimulated T cell proliferation and lymphokine secretion is decreased when the restricted numbers of monocytes/M phi are HIV 1 infected. There are, therefore, two possible roles of M phi in HIV infection and progression to disease. First, as a reservoir and vehicle for dissemination of the virus, and second, as an immune cell whose essential functions are impaired by infection.
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PMID:Decreased accessory cell function of macrophages after infection with human immunodeficiency virus type 1 in vitro. 225 85


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