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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interferon-alpha (IFN-alpha) is a naturally occurring cytokine that mediates numerous biological activities and has demonstrated therapeutic potential in a variety of malignancies. Encouraging activity against HIV-1 replication has also been observed with IFN-alpha in the treatment of AIDS, although hematotoxicity has been a frequently observed side effect. In addition, in vitro studies have suggested that IFN-alpha may function as a down-regulator of myelopoiesis. A recombinant hybrid of subtypes of human IFN-alpha, rHuIFN-alpha A/D, has antiviral activity in murine cells in vitro and in vivo. This study examines the effect of acute and subchronic exposure to rHuIFN-alpha A/D on hemopoietic and immune parameters in C57Bl/6 mice. IFN-alpha was administered ip at 0, 1000, 10,000, and 100,000 units/day for either 1 or 10 consecutive days. Many of the known effects of IFN-alpha in humans such as anemia, leukopenia, and thrombocytopenia were observed in mice following subchronic exposure, with the latter two effects also manifested following acute exposure. Further analysis showed that this leukopenia was not selective. Both splenic and bone marrow cells were examined following 10 days of dosing with the high dose of IFN-alpha. Lymphocytes were reduced in both compartments, while granulocytes were increased in both compartments. Bone marrow cells programmed to differentiate into granulocytes (CFU-G) were suppressed, while macrophage progenitors (CFU-M) were stimulated. Erythroid cells decreased in the marrow but increased in the spleen, suggesting that the microenvironment may play a significant role in the effect of IFN-alpha. The proliferative capacity of both B and T splenic lymphocytes was significantly suppressed in a dose-related fashion following multiple exposure to IFN-alpha. Clinically, IFN-alpha is most often given in multiple doses and the present data suggest that such a regimen is toxic to both erythroid and myeloid cells, as well as being immunotoxic to splenic B and T lymphocytes.
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PMID:Organ-specific hematopoietic changes induced by a recombinant human interferon-alpha in mice. 236 70

Levels of replication of HIV in two different populations of monocyte/macrophages (M/M) at different stages of maturation were evaluated, as well as the antiviral activity of alpha-interferon (alpha-IFN) and Ampligen (an inductor of endogenous production of alpha-IFN). HIV replication was found to be 5-10 times greater in mature than in young M/M. Furthermore, alpha-IFN and Ampligen showed a substantial anti-HIV activity in young M/M, while little effect was achieved in mature M/M. Finally, HIV replication in chronically-infected M/M was not affected by alpha-IFN. These results suggest that alpha-IFN might be useful in combination with other anti-HIV drugs in the therapy of HIV-related disease.
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PMID:[Inhibition of alfa interferon and ampligen of human immunodeficiency virus (HIV) replication in monocyte-macrophage subpopulations]. 238 Dec 79

Specific cellular immune responses to human immunodeficiency virus type 1 (HIV-1) were assessed in mononuclear leukocyte cultures from homosexual men with documented, early phase HIV-1 infection. Cell cultures from men with a mean duration of 1.3 yr (range, 0.3 to 2.2 yr) of HIV-1 infection were treated with UV-inactivated, whole, purified HIV-1 Ag together with various concentrations of rIL-2. Cell supernatants were harvested after 5-day incubation and assayed for IFN activity against encephalomyocarditis virus in human WISH cells. IFN subtypes were characterized by neutralization of antiviral activity with antiserum specific for human IFN-gamma and IFN-alpha. Results showed that cultures from 68% (17 of 25) of the HIV-1-seropositive subjects produced "immune" IFN-gamma in response to whole HIV-1 Ag plus rIL-2. IFN-gamma was induced in only 20% (5 of 25) of cultures treated with HIV-1 Ag alone. Enhancement of HIV-1-specific IFN-gamma production by rIL-2 was synergistic rather than additive in that titers induced by the mixture were consistently higher than the sum of IFN titers induced by HIV-1 or rIL-2 alone. This effect was not demonstrable in cultures from 18 HIV-1-seronegative men. Similarly, HIV-1-immune specific augmentation of IFN-gamma production by rIL-2 was noted for PENV9, a recombinant HIV-1 envelope glycoprotein gp41 and gp120 fragment. Production of IFN-gamma may be an important, HIV-1-immune specific parameter in the host response to this retrovirus.
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PMID:HIV-1-specific production of IFN-gamma and modulation by recombinant IL-2 during early HIV-1 infection. 245 86

The design of a prospective phase-II study on the treatment of Kaposi's sarcoma (KS) in patients with HIV infection is described. In this study the toxicity and antineoplastic activity of high-dose alpha-interferon (20 x 10(6) U/m2 s.c. daily) will be investigated in patients with advanced and progressive KS. Patients with progressing KS during IFN treatment or with relapsing KS after IFN will be treated with vinblastine (4 mg/m2 i.v., days 1, 8, and 15) and bleomycin (15 mg i.v., days 1 + 8). The study was only recently activated; results are so far not available.
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PMID:Treatment of advanced, progressive epidemic Kaposi's sarcoma (EKS): a phase-II study. 245 94

To determine the effects of immunomodulatory agents upon HIV replication in macrophages, cultured monocyte-derived macrophages were treated with various substances and then infected with a macrophage-tropic strain of HIV-1. Pretreatment with rIFN-alpha, IFN-beta, and IFN-gamma, or bacterial LPS prevented viral replication in macrophages. In treated cultures, little or no infectious HIV or p24 core antigen was released into the supernatant, no virions were seen by electron microscopy, no viral RNA or DNA was detectable in the cell lysates, and no cytopathology (as determined by multinucleated giant cell formation) occurred. In contrast, pretreatment with a wide dose range of recombinant IL-1 beta, IL-2, IL-4, IL-6, M-CSF, TNF, or lymphotoxin failed to protect macrophages from productive infection by HIV. A consistent effect of granulocyte/macrophage-CSF on HIV replication in macrophages was not observed. In dose response studies, pretreatment with approximately 100 U/ml of IFN-alpha, approximately 10 U/ml of IFN-beta, or approximately 100 U/ml of IFN-gamma was sufficient to prevent virion release maximally and to prevent cytopathology completely. In kinetic studies, IFN-alpha, IFN-gamma, or LPS were added to the macrophage cultures either before or after infection with HIV. Even when added 3 d after infection with a multiplicity of 1 50% tissue-culture infectious dose per cell, all three treatments markedly reduced virion release, suggesting that these agents act at a point in the viral life cycle beyond the early events of virus binding, penetration, and uncoating. These data indicate that HIV replication in previously uninfected macrophages may be regulated by an inducible host cell mechanism. These findings may explain the restricted replication of HIV in macrophages in vivo and suggest an antiviral role for interferons in the therapy of HIV infection.
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PMID:Interferons and bacterial lipopolysaccharide protect macrophages from productive infection by human immunodeficiency virus in vitro. 246 37

Promonocytic (U1) and T lymphocytic (ACH-2) cell lines chronically infected with human immunodeficiency virus type 1 (HIV-1) constitutively express low levels of virus, but expression can be induced by phorbol esters and cytokines. Whereas ACH-2 cells produce infectious virions, U1 cells produce defective, noninfectious particles. Although 3'-azido-3'-deoxythimidine (AZT) prevented acute HIV infection of susceptible cells, it did not prevent the induction of HIV expression in the infected cell lines. In contrast, interferon alpha (IFN-alpha) inhibited the release of reverse transcriptase and viral antigens into the culture supernatant after phorbol ester stimulation of both cell lines. Further, IFN-alpha suppressed the production or release (or both) of whole HIV virions, but had no effect on the amount of cell-associated viral proteins. Also, after phorbol ester stimulation of ACH-2 cells, IFN-alpha reduced the number of infectious viral particles secreted into the culture supernatant, but had no effect on the infectivity of cell-associated virus. These findings lend support to the combined use of antiviral agents that have action at both the early (AZT) and the late (IFN-alpha) stages of HIV replication.
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PMID:Interferon-alpha but not AZT suppresses HIV expression in chronically infected cell lines. 247 Jan 48

A comparative study of the replication kinetics of human immunodeficiency virus type 1 (HIV-1) was performed in the promonocytic U937 cells and in the T lymphoblastoid H9 cells. If a productive HIV-1 infection of both cell types could be established, the time which elapses before most of the cells could express viral proteins is always proportionally longer for U937 cells than for H9 cells. Indeed, when U937 cells are infected with HIV-1, this nonproductive phase is followed by a lag phase during which the percentage of virus-producing cells is slowly increasing when compared to H9 cells. The restriction of HIV-1 replication in U937 cells might be consecutive to the lower adsorption of viral particles to these cells, even though the same percentage of U937 and H9 cells was expressing the CD4 molecule. Furthermore, we demonstrate that HIV-1 replication in U937 cells is mainly restricted by endogenous IFN-alpha. Indeed, addition of anti-IFN-alpha antibodies at the time of infection, during the nonproductive phase of the viral replication cycle, or during the lag phase leads to an earlier expression of viral proteins and/or to a rapid increase in the percentage of virus-producing cells. Likewise, the treatment of cultures of HIV-1 chronically infected U937 cells with the same antibodies induces an increased production of viral particles. Thus, IFN-alpha appears to be involved in the persistence of HIV-1 in the monocytes/macrophages of infected individuals.
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PMID:Restriction of HIV-1 replication in promonocytic cells: a role for IFN-alpha. 249 97

beta-Interferon (IFN-beta) was evaluated prospectively for its antiviral activities in early stage human immunodeficiency virus (HIV) infection. Ten patients with hemophilia and HIV infection [8 asymptomatic carriers (AC) and 2 AIDS-related complex (ARC)] were intravenously injected with 1 million IU of IFN-beta twice a week for 6 months. For comparison, seven patients (six AC and one ARC) with hemophilia and HIV infection were observed for the same time period without any drugs. One episode of localized herpes zoster each occurred during the trial in the IFN group and in the control group. There were no significant differences in the absolute number of CD4+ lymphocytes and ratios of CD4+/CD8+ lymphocytes between the two groups. Recipients had flu-like symptoms but no serious toxicities. No clinical and immunological benefits to patients with early stage HIV infection were observed during the 6 months of treatment.
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PMID:Beta-interferon and early stage HIV infection. 249 47

High levels of an acid-labile IFN-alpha have been demonstrated in the sera of patients with symptomatic HIV infection. IFNs have been shown to enhance the cytotoxic and antiproliferative actions of tumor necrosis factor (TNF), which is a potent mediator of inflammation and sepsis. We show that the acid-labile IFN-alpha present in AIDS sera can induce TNF synthesis and sensitize blood monocytes (BM) to endotoxin stimulation resulting in further synthesis of TNF in vitro. TNF production by BM from patients with HIV infections and normal controls was measured by a cytotoxicity assay on L929 cells using human TNF alpha as a standard. BM from AIDS patients spontaneously produce high levels of TNF and are hypersensitive to endotoxin stimulation, resulting in enhanced synthesis of TNF. In determining the mechanism involved, we demonstrated that treatment of normal BM with AIDS sera results in induction of TNF. Neutralization of the acid-labile IFN-alpha in AIDS sera with polyclonal anti-IFN-alpha antibodies results in diminution of TNF induction. In addition, pretreatment of normal BM with AIDS sera, IFN-alpha, or IFN-gamma renders the cells hypersensitive to endotoxin. Consequently, activation of the TNF system by the acid-labile IFN-alpha contributes to some of the physiological disturbances, such as the wasting syndrome, and to the pathophysiology of sepsis in AIDS patients.
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PMID:Endotoxin induction of tumor necrosis factor is enhanced by acid-labile interferon-alpha in acquired immunodeficiency syndrome. 250 43

Serum and cerebrospinal fluid (CSF) levels of interleukin-2 (IL-2), soluble IL-2 receptor (sIL-2R), and gamma-interferon (gamma-IFN) were measured in multiple sclerosis (MS) patients, human immunodeficiency virus type 1 (HIV-1)-infected patients and normal controls (NC). Increased levels of both IL-2 and sIL-2R were found in MS serum. Moreover, 11 of 50 MS patients showed detectable levels of IL-2 in the CSF. HIV-1-infected patients had increased levels of sIL-2R in serum and, less frequently, in the CSF. gamma-IFN was never detected in serum and CSF of all the patients studied. These findings confirm preliminary reports, further stress a systemic T-cell activation in MS, and support the hypothesis that an immunologic disorder exists in such patients.
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PMID:Immune activation in multiple sclerosis: study of IL-2, sIL-2R, and gamma-IFN levels in serum and cerebrospinal fluid. 250 88


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