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Query: UMLS:C0001175 (AIDS)
 120,706 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The recently described acquired immune deficiency syndrome (AIDS) is characterized by the occurrence of severe opportunistic infections and an aggressive form of Kaposi's sarcoma. A variety of profound defects in cell-mediated immunity have been reported in association with the AIDS, including deficiencies in natural killer (NK) cell activity and cytomegalovirus (CMV)-specific cytotoxicity. In the present study, the in vitro effects of interleukin-2 (IL-2) and interferon beta (IFN Beta) on these abnormalities were examined to assess the potential use of these lymphokines in the immunotherapeutic treatment of this syndrome. The peripheral blood lymphocytes (PBL) from six male homosexuals with AIDS and an active CMV infection exhibited markedly depressed NK cell and CMV-specific cytotoxic lymphocyte responses compared with uninfected, heterosexual control subjects. Incubation of PBL with IFN Beta enhanced the NK cell activity and the CMV-specific cytotoxicity of only one of six and neither of two AIDS patients, respectively, while enhancing the NK cell activity of all six control subjects. In contrast, IL-2 dramatically enhanced both the NK cell and the CMV-specific cytotoxic lymphocyte activities of all of the patients. These results indicate that IL-2 can substantially potentiate the depressed cytotoxic effector functions of PBL from AIDS patients, while IFN Beta has little effect.
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PMID:Interleukin-2 enhances the depressed natural killer and cytomegalovirus-specific cytotoxic activities of lymphocytes from patients with the acquired immune deficiency syndrome. 630 51

We have examined the numbers of the total T (T11+) cells, T-helper (T4+) cells, T-suppressor (T8+) cells, NK cells (Leu7+), and the functional integrity of T, B, and NK cells in healthy male heterosexuals and compared the data to those obtained from AIDS patients and male homosexuals at risk. The absolute number of total T (T11+) and T-helper (T4+) cell populations were significantly reduced among most of the asymptomatic homosexual males and even more decreased in the AIDS patients. By contrast, the absolute numbers of T-suppressor cells (T8) remained virtually unaltered in the three study populations. The absolute numbers of circulating natural killer cells were similar in the controls and the homosexual subjects, but significantly reduced in the AIDS patients. Proliferative responses to T-cell mitogen (PHA) and T-cell dependent B-cell mitogen (PWM) were severely impaired in prodromal subjects and more so in the AIDS group. Response to PWM was unrelated to the total number of T-suppressor cells, but was associated with a significant decrease in T-helper cell number. Furthermore, all AIDS patients exhibited a significantly depressed NK-cell activity that could not be normalized by addition of alpha IFN or IL-2 and in most cases correlated with the reduced absolute number of NK (Leu7+) cells as well as T-helper cells (T4) and T4/T8 ratios. Three distinctive subgroups with normal (N-NK), significantly heightened (H-NK), and markedly lowered (L-NK) NK activity could be readily identified among the homosexual male population at risk. The N-NK and L-NK groups displayed marginal to no response to in vitro treatment with alpha IFN and interleukin-2. The NK-cell activity, however, in the H-NK group was moderately to strongly inhibited by inclusion of the two immunomodifiers.
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PMID:Functional integrity of T, B, and natural killer cells in homosexual subjects with prodromata and in patients with AIDS. 633 53

Healthy hemophiliacs receiving antihemophilic (AHF) concentrates have decreased T-helper/suppressor (H/S) ratios, similar to the changes observed in healthy homosexuals considered at risk for the acquired immune deficiency syndrome (AIDS). We present a hypothesis which focuses on the role of natural killer (NK) cells and elevated serum levels of alpha interferon (IFN alpha) in hemophiliacs with AIDS. This hypothesis suggests that alloantigens in AHF concentrates provide an important inducing event which compromises the immune system of the hemophilia patient and enhances his susceptibility to infection by a transmissible agent. It provides an explanation for the predominance of NK cells with T-cell markers, impaired NK cell function, elevated serum IFN alpha levels, and the deficit in T-helper/inducer cells in hemophilic patients with AIDS. Furthermore, it could account for the T-cell subset imbalance in relation to total AHF units transfused, and to the development of an inverted H/S ratio which is a constant feature of AIDS.
AIDS Res
PMID:The acquired immune deficiency syndrome (AIDS) in hemophiliacs: a hypothesis. 644 28

Recent research indicates that the proopiomelanocortin derivative alpha-melanocyte stimulating hormone (alpha-MSH) is a significant modulator of host reactions including fever and inflammation. Although the precise mechanism of action is still unknown, cytokine antagonism is believed to be responsible for at least a part of its anti-inflammatory/antipyretic influence: alpha-MSH antagonizes pyrogenic and proinflammatory effects of cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor (TNF), and interferon gamma (IFN gamma). Although it is clear that the peptide can act within the brain to inhibit fever and peripheral inflammation, an anti-inflammatory effect on a peripheral target was evidenced in animals with transection of the spinal cord. Recent data show that alpha-MSH is significant also in human disorders such as AIDS, rheumatoid arthritis, and myocardial infarction. This molecule is believed to be a key factor in neuroimmunomodulation and it may be useful as a therapeutic agent in control of inflammatory reactions.
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PMID:The neuropeptide alpha-melanocyte-stimulating hormone: a key component of neuroimmunomodulation. 748 26

Preclinical and clinical studies with an azidothymidine (AZT)/interferon-alpha (IFN-alpha) combination resulted in a marked and synergistic antiretroviral activity. The administration of the two drugs in HIV-seropositive patients affected with Kaposi's sarcoma, however, induced neutropenia, thrombocytopenia, and, in some cases, anemia. A possible means to improve the therapeutic index of AZT and/or IFN-alpha in AIDS patients could be the addition of hematopoietic growth factors. In vitro activity of cytokines on the hematotoxicity of the AZT-IFN-alpha association has not yet been studied. We have performed an in vitro study to evaluate the toxicity of AZT, IFN-alpha, or both on peripheral blood hematopoietic progenitors (CFU-GM and BFU-E) and to assess the activity of interleukin 1 (IL-1), granulocyte-macrophage colony-stimulating factor (GM-CSF), or both in modifying AZT-IFN-alpha hematotoxicity. Results indicate that AZT, IFN-alpha, and combinations of the two have a dose-dependent inhibitory effect on the in vitro growth of peripheral blood hematopoietic progenitors. Combinations of AZT and IFN-alpha inhibited CFU-GM and BFU-E proliferation in an additive manner. Neither IL-1 nor GM-CSF alone was able to induce a significant reduction of AZT-induced damage. Only the addition to the cultures of both cytokines partially curbed the antiproliferative activity of AZT at low dosages.
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PMID:Azidothymidine and interferon-alpha in vitro effects on hematopoiesis: protective in vitro activity of IL-1 and GM-CSF. 749 65

Dysmorphic marrow morphology and bone marrow failure are common in AIDS patients, but the mechanism of HIV-1 effects on blood cell production is unclear. Experiments to test the susceptibility of hematopoietic progenitor cells to HIV-1 infection have led to conflicting results. We found that hematopoietic colony formation by burst-forming units-erythroid and CFU-GM was equivalently inhibited by both active and heat-inactivated, noninfectious virus. Inhibition was dependent on the presence of macrophages and was not observed in cultures derived from highly enriched CD34+ cells. We hypothesized that TNF-alpha, produced by mononuclear phagocytes after contact with HIV-1 or gp120 and itself a potent suppressor of hematopoiesis, might mediate this effect. The addition of anti-TNF-alpha neutralizing Abs to marrow cultures abrogated inhibition by gp120 or virus. In contrast, neutralizing Abs to Il-4, IFN-alpha, and TGF-beta failed to improve colony formation. TNF-alpha was released from blood monocytes and marrow mononuclear cells stimulated by gp120. TNF-alpha is increased in the blood of patients with late stage AIDS and may mediate many of the symptoms of the disease. Our data do not support a requirement of direct infection of hematopoietic progenitor cells by HIV-1 for the inhibition of hematopoiesis in vitro. We propose instead an indirect mechanism of viral suppression of hematopoiesis as a result of TNF-alpha induction by virus or viral envelope glycoprotein. The importance of local TNF-alpha production in patients' marrow is amenable to clinical testing.
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PMID:HIV-1 suppression of hematopoiesis in vitro mediated by envelope glycoprotein and TNF-alpha. 752 21

Delavirdine (bisheteroarylpiperazine, U-90152), a nonnucleoside reverse transcriptase inhibitor of human immunodeficiency virus type 1 (HIV-1), was evaluated in a two-drug combination with recombinant human interferon-alpha (IFN-alpha) or the peptidomimetic protease inhibitor U-75875 against HIV-1 replication in vitro. Viral growth was assayed in a CD4+ T cell line (H9) infected with HIVIIIB and in human peripheral blood mononuclear cells infected with the clinical isolate HIVJRCSF. Drug synergy, estimated by the combination index method and the method of Pritchard and Shipman, was observed when delavirdine was combined with U-75875 or IFN-alpha over a range of drug concentrations (delavirdine: 0.001, 0.003, 0.01, 0.03 microM; U-75875: 0.01, 0.03, 0.1, 0.3, 1.0 microM; IFN-alpha: 2, 6, 17, and 50 or 10, 30, 100, and 300 IU/mL). The combinations showed no detectable drug antagonism or cytotoxicity. These in vitro synergy data support the potential use of delavirdine with either a protease inhibitor or IFN-alpha in patients with AIDS.
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PMID:In vitro inhibition of human immunodeficiency virus type 1 by a combination of delavirdine (U-90152) with protease inhibitor U-75875 or interferon-alpha. 752 53

Cellular adhesion molecules, such as ICAM-1, -2, and -3; LFA-1; and HLA class I and II are incorporated into HIV-1 virions during budding from infected cells. These virion-associated molecules can be involved in the adsorption to susceptible cells displaying the corresponding counterligands. A number of cytokines have been shown to upregulate the cellular expression of adhesion molecules, such as ICAM-1 and HLA-DR. In this study we investigated the effects of IFN-gamma on the incorporation of ICAM-1, LFA-1, and HLA-DR into mature HIV-1 progeny from chronically infected cells. The ability of such virus progeny to infect either CD4-positive or -negative cells was also investigated. The results indicate that IFN-gamma stimulates the expression of ICAM-1 and of HLA-DR on HIV-1-infected cells, whereas LFA-1 expression is unaffected. The same modifications were also observed on virus progeny, because specific MAbs to ICAM-1 and HLA-DR captured infectious HIV-1 from IFN-treated cells with higher efficiency as compared to virus from control cells, whereas virus binding to anti LFA-1 MAb was unchanged. Moreover, the HIV-1 progeny released from IFN-treated cells showed an increased ability to bind to and to infect CD4-negative cells, whereas the infectivity was basically unchanged for CD4-positive cells. Our results suggest that cytokines, as well as other soluble factors, may expand the host cell range of HIV-1, possibly through modifications of the cell-derived surface molecules on the virions.(ABSTRACT TRUNCATED AT 250 WORDS)
AIDS Res Hum Retroviruses 1995 May
PMID:HIV type 1 grown on interferon gamma-treated U937 cells shows selective increase in virion-associated intercellular adhesion molecule 1 and HLA-DR and enhanced infectivity for CD4-negative cells. 757 10

A randomized, placebo-controlled trial was designed to evaluate safety and immunogenicity of an anti-cytokine vaccine in high risk HIV-positive patients. This strategy was aimed to modulate the impaired cytokine regulation in AIDS. Twelve asymptomatic patients on antiretroviral therapy for at least 1 year and with CD4 cell counts between 100-300/mm3 were randomized to receive adjuvanted formol-inactivated interferon alpha-2a (IFN alpha) and continue the current antiretroviral treatment, whatever it was, or to receive the adjuvant alone and the current antiretroviral treatment. All patients received 4 i.m. injections monthly, followed by booster injections every 3 months. Clinical status, immunology and virology were monitored. Immune response to vaccination was evaluated in term of antibody detection (ELISA) and serum anti-IFN alpha neutralizing capacity. Only local discomfort and transient fever were reported. All vaccines except one showed increased levels of anti-IFN alpha Abs and developed serum IFN alpha neutralizing capacity. Viral load did not increase in vaccinees while it remained unchanged or even increased in placebo-treated patients. None of them showed HIV-related symptoms and all had their CD4 cell counts stabilized over 18 months, whereas 2 placebo-treated patients developed full-blow AIDS. In conclusion, anti-IFN alpha vaccine was safe and immunogenic. Stable clinical and immunological status over 18 months was observed in vaccinees coupled to increased serum IFN alpha neutralizing capacity.
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PMID:Anti-alpha interferon immunization: safety and immunogenicity in asymptomatic HIV positive patients at high risk of disease progression. 758 Aug 31

Cytotoxicity mediated by natural killer (NK) and lymphokine-activated killer (LAK) cells may be of significance in host defense against viral infections. This study included 347 patients infected with human immunodeficiency syndrome virus (HIV) type 1 and 110 controls. The NK cell activity, either unstimulated or stimulated with interferon-alpha (IFN-alpha) or interleukin-2 (IL-2), and the LAK cell activity were suppressed in patients, but the NK/LAK cell activity did not differ between patients with AIDS and patients without AIDS. However, the IFN-alpha-stimulated NK cell activity and LAK cell activity were reduced in patients with symptoms of HIV disease (CDCIV) when compared with asymptomatic patients (CDCII+III). When the data were analyzed by multiple linear regression, the percentage of CD4+ cells had a positive effect on these two parameters in patients without AIDS, whereas the percentage of CD4+ cells had no significant effect on unstimulated and IL-2-stimulated NK cell activity in these patients. In controls and AIDS patients, the percentage of CD4+ cells had no effect on NK/LAK cell activity in multiple linear models. The total number of CD16+ cells was low in patients compared to controls, whereas the percentages of CD16+, CD56+, and CD16+CD56+ were either normal or elevated. Therefore, the decrease in NK cell subpopulations did not contribute to the observed depression in NK/LAK cell activity in vitro. It is concluded that natural immunity is suppressed in HIV-seropositive patients primarily because of a qualitative defect of the NK/LAK cells. This qualitative defect includes a reduced responsiveness to IFN-alpha, which is progressive until the onset of symptoms, and possibly related to the loss of CD4+ cells.
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PMID:Defective natural immunity: an early manifestation of human immunodeficiency virus infection. 765 Apr 85


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