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

Infection of immune cells with HIV induces dysregulation of cytokines which may play a vital role in HIV pathogenesis. We analysed the expression of T helper type 1 (Th1) (interferon-gamma (IFN-gamma)) and Th2 (IL-4, IL-10) type cytokines in peripheral blood lymphocytes (PBL) from HIV+ patients. The semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) analysis revealed that IFN-gamma mRNA in unstimulated PBL was significantly decreased and IL-10 mRNA was significantly upregulated in patients with < 400 CD4+ T cells/mm3 (n = 30) as compared to patients with > 400 CD4+ T cells/mm3 (n = 6) and normal controls (n = 16). In addition, IL-10 mRNA levels were inversely associated with IFN-gamma expression. Similar results were obtained by measuring IL-10 production in the supernatants of PBL cultured in vitro without stimulation by employing an enzyme immunosorbent assay (ELISA). However, the levels of IL-4 and IFN-gamma produced by unstimulated PBL were undetectable by ELISA. Mitogen stimulation of PBL revealed two groups of HIV+ individuals based on IL-10 production. PBL from one set of individuals produced low levels of IL-10 (low IL-10 producers) whereas the other group produced IL-10 comparable to that of normal controls (IL-10 producers). Production of IL-4 was significantly reduced in HIV+ individuals with < 400 CD4+ T cells/mm3 as compared to the normal controls. However, ability to produce IFN-gamma by mitogen-stimulated total PBL and CD4+ purified cells was not impaired in HIV+ individuals. These results suggest that unstimulated and mitogen-stimulated PBL of HIV+ individuals exhibit dysregulation of Th2 type cytokines which may play a role in HIV immunopathogenesis.
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PMID:Expression of IL-10, IL-4 and interferon-gamma in unstimulated and mitogen-stimulated peripheral blood lymphocytes from HIV-seropositive patients. 755 96

HIV-specific cytotoxic T lymphocytes (CTLs) are an important component of the host immune response against HIV infection, and these cells release a variety of cytokines when they meet their target antigen. Since the phosphodiesterase inhibitor pentoxifylline is being used as a therapeutic agent in clinical trials of HIV infection due to its inhibitory effect on virus replication in vitro, we examined the effect of pentoxifylline on cytotoxicity and cytokine secretion by HIV-specific CD8+ CTLs. Pentoxifylline inhibited cytotoxicity of CTLs and suppressed interferon-gamma, tumor necrosis factor-alpha, and granulocyte-macrophage colony-stimulating factor release by these cells at the transcription level. Suppression of cytokine release resulted in reduced capacity of the CTLs to induce HLA class I and ICAM-1 expression and to stimulate HIV-1 replication. These results suggest that inhibition of HIV-specific CD8+ CTLs by pentoxifylline may be therapeutically relevant. Moreover, this study extends previous observations by demonstrating that, in addition to its ability to suppress cytokine production by macrophages and CD4+ T helper cells, pentoxifylline may inhibit cytotoxicity and cytokine secretion by antigen-specific CD8+ cytotoxic T lymphocytes.
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PMID:Inhibition of cytotoxicity and cytokine release of CD8+ HIV-specific cytotoxic T lymphocytes by pentoxifylline. 758 37

Individual cells capable of interferon-gamma (IFN-gamma) synthesis are easily detected by immunofluorescence and flow cytometric analysis using an anti-IFN-gamma monoclonal antibody as specific reagent. By IFN-gamma flow cytometry assay, we demonstrated that HIV-seropositive patients, starting at the early stage of viral infection, generally have an increased percentage of lymphocytes potentially able to produce IFN-gamma, compared with healthy blood donors. IFN-gamma expression in patient lymphocytes was observed to increase with the progressive stages of HIV infection, with the highest figures occurring in stage C patients. Such increased IFN-gamma expression involved both CD4+ and CD8+ T cell subsets. Most interestingly, we found patients at the same stage of HIV infection who had similar numbers of total and CD4+ lymphocytes but highly different percentages of lymphocytes potentially capable of producing IFN-gamma.
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PMID:CD4+ and CD8+ lymphocytes of patients with AIDS synthesize increased amounts of interferon-gamma. 758 43

Human hepatocellular carcinoma (HCC) cell lines, HEP-G2, J5, and SK-HEP-1, which differ in their differentiation status, were compared for their trans-activating activities after treatment with cytokines or 12-O-tetradecanoylphorbol-13-acetate (TPA). These cells were transfected with a long terminal repeat (LTR) which was derived from human immunodeficiency virus type 1 (HIV-1) and ligated to chloramphenicol acetyl transferase (CAT) gene. After treatment with interleukin-1 alpha (IL-1 alpha), interleukin-6 (IL-6), interferon-gamma (IFN-gamma), or TPA, they exhibited various degrees of enhancement of transactivation. The well differentiated HEP-G2 cells exhibited the highest degree of enhancement with these agents, while the poorly differentiated SK-HEP-1 cells showed no enhancement with cytokines and slight enhancement with TPA. The J5 cells, which were intermediate in their status of differentiation, showed a moderate degree of enhancement with cytokines and TPA. These results suggest that HCC cells at different stages of differentiation may produce different levels of cellular transacting factors activated by each of these agents. To map the cytokine response elements (CREs) in the HIV-1-LTR, HEP-G2 cells were transfected with nested series of 5' deletion mutants of HIV-1-LTR and treated with each of these cytokines. It was found that not only the degrees but also the patterns of enhancement varied depending upon the presence of positive or negative regulatory sequences in HIV-1-LTR, and that the NF-kappa B sequence played an important role, either by itself or in conjunction with the 5'-proximal response elements (REs) to interact with cellular trans-activating factors elicited by the cascade of transduction responses to cytokines. Despite the presence of promoters including kappa B and IFN-gamma RE as well as IL-6RE sequence in HIV-1-LTR-transfected cells, the poorly differentiated SK-HEP-1 cells showed no enhancement of transactivation by these cytokines, suggesting the lack of receptors or activity of some signal transduction factors which are present in well differentiated HEP-G2 and moderately differentiated J5 cells.
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PMID:Cytokine regulation of HIV-1 LTR transactivation in human hepatocellular carcinoma cell lines. 762 43

HIV-infected patients are defective in their ability to produce interleukin (IL)-12 in vitro in response to pathogenic bacteria and parasites. IL-12 enhances the patient's depressed natural killer cell cytotoxic activity, peripheral blood lymphocyte production of interferon-gamma (IFN-gamma), and proliferative T cell response in vitro to recall antigens, HIV antigens, alloantigens, and mitogens. However, these effects represent short-lived responses and imply the need for chronic IL-12 therapeutic administration in the clinical setting. To identify any long-term effects of IL-12 on T cell differentiation toward Th1 cells, peripheral blood T cells from 10 HIV-infected patients at different stages of disease were cloned by limiting dilution in the presence or absence of IL-12 and tested for cytokine production in response to stimulation with anti-CD3 antibodies and phorbol diesters IL-12 present during the first 2 wk of clonal expansion determined a stable severalfold enhancement on the ability of both CD4+ and CD8+ clones to produce IFN-gamma. Because priming for high IFN-gamma production is probably the most important mechanism by which IL-12 induces generation of efficient T helper type 1 (Th1) cells, these results suggest the possibility that IL-12 treatment in vivo of HIV-infected patients may stimulate a protective Th1 response against opportunistic pathogens and possibly HIV itself.
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PMID:Priming for high interferon-gamma production induced by interleukin-12 in both CD4+ and CD8+ T cell clones from HIV-infected patients. 765 39

Interferon inhibits expression of human immunodeficiency virus type-1 (HIV-1) through unknown mechanisms. A gene inducible by interferon-alpha (IFN-alpha) and interferon-gamma (IFN-gamma) was isolated by screening of a human complementary DNA library for proteins binding to the Rev-responsive element (RRE) of HIV-1. The product of this gene, RBP9-27, was shown to bind RNA in vitro and to inhibit HIV-1 expression after transfection into human cells. RBP9-27 primarily inhibited Rev-dependent posttranscriptional steps of viral gene expression. Thus, RBP9-27 is a cellular factor that antagonizes Rev function. These results suggest an interferon-induced antiviral mechanism operating through the induction of RNA binding proteins such as RBP9-27. Elucidation of RBP9-27 function may lead to a better understanding of the mechanism of interferon action during HIV-1 infection.
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PMID:Inhibition of Rev-mediated HIV-1 expression by an RNA binding protein encoded by the interferon-inducible 9-27 gene. 816 5

Visceral leishmaniasis (kala-azar) affecting HIV-infected patient is being reported in increasing frequency. A 40-year-old German bisexual patient with full-blown AIDS is described who presented with Kaposi's sarcoma, epigastric pain, diarrhea, and weight loss but without fever. Leishmania amastigotes were initially found in biopsies from stomach, duodenum, and a cutaneous Kaposi's sarcoma lesion but were later also recovered from bone marrow and lymph node. The patient received three courses of a combination of pentavalent antimony and interferon-gamma. In addition to the common side effects such as fever, thrombocytopenia, and elevated amylase and lipase, a vivid progression of the Kaposi's sarcoma was noted. Tumor progression was temporally closely associated with treatment with interferon-gamma. Because this phenomenon has also been observed in other patients, we advise caution when using interferon-gamma in patients with Kaposi's sarcoma.
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PMID:Treatment of atypical leishmaniasis with interferon gamma resulting in progression of Kaposi's sarcoma in an AIDS patient. 771 12

Organisms belonging to the Mycobacterium avium complex (MAC) are common pathogens in immunosuppressed and AIDS patients. This paper reviews the role of cytokines in the pathogenesis of MAC infection. MAC organisms mainly infect monocytes and macrophages, and the effect of HIV infection on susceptibility of macrophages to MAC infection is largely unknown. Both GM-CSF and tumour necrosis factor-alpha can induce mycobacteriostatic/mycobactericidal activity in MAC-infected macrophages. The activity of interferon-gamma on mycobacterial infection appears to be dependent on the type of macrophage: in murine peritoneal and human monocyte-derived macrophages, interferon-gamma does not inhibit the intracellular growth of MAC, whereas in intestinal macrophages interferon-gamma results in inhibition of MAC. Transforming growth factor-beta 1, interleukin-10 and interleukin-6 have all been shown to counteract the immunoactivating cytokines and MAC survival may be due to induction of these inhibitory cytokines within the macrophage. GM-CSF has been given to patients with disseminated MAC infection. Isolated macrophages from these patients demonstrated increased superoxide anion production and enhanced mycobacteriostatic/cidal activity compared with macrophages isolated from the same patients before GM-CSF treatment. These results suggest that GM-CSF may have potential in the treatment of MAC infection.
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PMID:Potential role of cytokines in disseminated mycobacterial infections. 787 49

Several peptides were synthesized, based on sequences of the HTLV-IIIB, HTLV-IIRF, and HTLV-IIIMN strains. These corresponded to the V3 region, the killer T cell activating site, the constant region of env, gag region protein and the helper T cell activating site. Some of these peptides were coupled to keyhole limpet hemocyanin (KLH), and some of them were polymerized with m-maleimido benzoyl-N hydroxysuccinimide ester (MBS). These peptides were used to immunize rabbits and mice. Antisera from immunized animals showed good levels of inhibition of CD4-dependent cell fusion by in vitro HIV infection. The antisera also inhibited the production of p24 protein in the HIV-infected culture system. Interestingly, a strong synergistic HIV growth inhibition by antiserum was observed when we immunized animals with multicomponent vaccine. In addition, substantial levels of HIV antigen-specific IL-2 producing and interferon-gamma (IFN-gamma) producing cells were also observed in lymph node cells from vaccinated mice. These results suggest that immunization with multicomponent vaccine can induce high levels of humoral antibodies as well as activate HIV-specific cellular immunity.
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PMID:Strong synergistic effects of multicomponent vaccine for human immunodeficiency virus infection. 787 54

The potential for eliciting humoral and cytotoxic T lymphocyte (CTL) responses to HIV-1 gp120 by gene gun-based DNA immunization in mice was examined. We speculated that the induction of de novo antigen production in the epidermis of BALB/c mice following particle bombardment-based gene delivery would result in both MHC class I- and class II-mediated antigen presentation for the elicitation of CTL and antibody responses, respectively. Following epidermal delivery of microgram quantities of an expression plasmid, gp120 production resulted in the appearance of MHC class I-restricted, CD8+ CTL responses. gp120-specific CTL responses peaked following a booster immunization, then declined with the appearance of gp120-specific IgG responses when additional booster immunizations were administered. This qualitative progression in the nature of gp120-specific immune responses with subsequent immunizations was paralleled by a simultaneous shift in the interferon-gamma and interleukin 4 release profiles following antigen stimulation of splenocytes in vitro. The simultaneous shifts in immune responses and cytokine release profiles indicate that the progression of antigen-specific CTL and IgG responses in gp120 DNA-immunized mice may be mediated through changes in the in vivo production of cytokines, such as those associated with the Th1 and Th2 subsets of CD4+ cells.
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PMID:A qualitative progression in HIV type 1 glycoprotein 120-specific cytotoxic cellular and humoral immune responses in mice receiving a DNA-based glycoprotein 120 vaccine. 788 98


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