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

Evidence has been presented for the involvement of various cytokines, including interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-alpha, in the pathogenesis of human immunodeficiency virus (HIV) infection. Since measured plasma levels may poorly reflect in vivo production of cytokines, we adopted in situ hybridization with cDNA oligonucleotide probes to enumerate blood mononuclear cells (MNCs) expressing mRNA for IL-6, IL-10, TNF-alpha, and perforin. The HIV-infected patients had elevated levels of MNCs expressing mRNA for all four cytokines compared to healthy controls. Numbers of IL-6 mRNA-expressing cells were higher in patients with clinical AIDS than in asymptomatic seropositive patients, and correlated inversely with CD4+ cell counts in blood, reflecting the involvement of IL-6 in later stages of HIV infection. The described approach could be an alternative way to study cytokines in HIV infection.
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PMID:Increased mRNA expression of IL-6, IL-10, TNF-alpha, and perforin in blood mononuclear cells in human HIV infection. 762 24

The effects of cysteamine (2-aminoethanethiol, MEA) and its disulfide, cystamine, on the human immunodeficiency virus (HIV-1) expression in chronically infected promonocytic cells (U1), T cell line (ACH-2), and peripheral blood monocyte-derived macrophages (MDM) were investigated. U1 and ACH-2 cells constitutively express low levels of virus, which is increased by the addition of tumor necrosis factor (TNF-alpha), interleukin 6 (IL-6), granulocyte-macrophage-colony-stimulating factor (GM-CSF), and other inducers. Cystamine, in noncytotoxic doses, suppressed in a concentration-dependent fashion the induction of HIV-1 expression mediated by TNF-alpha, IL-6, GM-CSF, and monokine-enriched monocyte culture supernatants in both U1 and ACH-2 cells as determined by HIV-1 reverse transcriptase (RT) activity. Similarly, HIV-1 expression was substantially reduced in the cystamine-treated primary MDM cultures compared with the untreated control cultures. The addition of cystamine into HIV-1 chronically infected MDM (12 days after infection was established) also suppressed 80-90% of RT activity in comparison to the untreated controls. HIV-1 (Bal) infected MDM cultures (without cystamine treatment) demonstrated giant syncytium formation, whereas cystamine-treated cultures lacked the giant syncytia induced by HIV-1 infection. Cystamine also inhibited LPS-induced TNF production in MDM. In contrast to cystamine, cysteamine showed no significant effects on either the monokine-induced HIV-1 expression in U1 or ACH-2 or acute and chronic HIV-1 infection in MDM.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cystamine inhibits HIV type 1 replication in cells of monocyte/macrophage and T cell lineages. 763 61

Individuals infected with Toxoplasma gondii normally develop resistance to the parasite, resulting in an asymptomatic chronic infection. In AIDS patients, this resistance is lost leading to reactivation of infection and development of encephalitis. To characterize the cytokine response of T. gondii-infected individuals, PBMC were cultured in vitro in the presence or absence of crude tachyzoite Ags (STAg). When stimulated with STAg, PBMC from T. gondii-infected donors, but not controls, produced high levels of Type 1 lymphokines (IL-2 and IFN-gamma) as well as the monokine IL-12, in the absence of detectable Type 2 lymphokines (IL-4 and IL-5). In contrast, cells of individuals from both groups produced high levels of IL-1, IL-6, and TNF-alpha when exposed to the same Ag preparation. By using highly purified elutriated cells, we demonstrated that monocytes are a major source of these monokines. The above findings were further expanded by analyzing the cytokine responses induced by STAg in PBMC from patients co-infected with T. gondii and HIV. Our results demonstrate that parasite-specific IL-2 and IFN-gamma responses are greatly impaired even before AIDS development, as is IL-12 synthesis by PBMC from HIV-infected individuals stimulated with STAg. In contrast, the release of IL-6 and TNF-alpha triggered by STAg is either not affected or augmented during HIV infection.
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PMID:HIV infection suppresses type 1 lymphokine and IL-12 responses to Toxoplasma gondii but fails to inhibit the synthesis of other parasite-induced monokines. 763 18

Kaposi's sarcoma (KS) is both an AIDS-defining disease and the most common HIV-associated malignancy. A cytokine-mediated pathogenesis for AIDS-KS is implicated because AIDS-KS-derived cell strains both respond to and express a variety of cytokines. We have reported the establishment of several (n = 18) AIDS-KS cell strains and determined that reduced exogenous growth factors are necessary to sustain proliferation in isolates from high histologic grade KS lesions. This current investigation explored the possibility that there are histologic grade-associated differences in either the qualitative and/or quantitative constitutive release of AIDS-KS growth stimulatory cytokines. Our findings showed that the incorporation of HTLV-II cytokine-rich conditioned media induced both qualitative and significant quantitative cytokine release, suggesting that exogenous growth promoters stimulate constitutive cytokine release. ELISA of our AIDS-KS cell strains demonstrated constitutive release of IL-6 (seven of seven), FGF-2 (five of seven), GM-CSF (three of seven), and IL-1 beta (one of seven). None of our AIDS-KS cell strains constitutively released detectable levels of Onco-M, IL-4, PDGF, TNF-alpha, or TNF-beta. In addition, we report that the method of cytokine result quantitation significantly affects reported cytokine levels. We determined that there was no significant histologic grade-dependent difference in the constitutive release of soluble cytokines by in vitro grown cultures of AIDS-KS cells. The presence of HIV influenced the sera cytokine profiles by elevating IL-6 and decreasing PDGF concentrations of HIV+ individuals relative to HIV- healthy controls. However, the presence of KS was not associated with unique serum cytokine profiles, because no differences were noted in comparisons of HIV+/KS+ versus HIV+/KS- individuals. Our findings suggest that the local environment is key in modulating AIDS-KS cytokine expression and that KS growth-promoting factors function at the local or paracrine, not the systemic, level. In conclusion, our previous results demonstrated a histologic grade-associated difference in the in vitro growth capacity of AIDS-KS cells; with high histologic grade isolates displaying a marked growth advantage during culture in minimally supplemented media. Findings from this current study reveal that although the potential for a constitutive growth loop exists in the high-grade isolates, it is not reflected in the free levels of soluble cytokines secreted into the culture medium.
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PMID:Comparison of constitutive cytokine release in high and low histologic grade AIDS-related Kaposi's sarcoma cell strains and in sera from HIV+/KS+ and HIV+/KS- patients. 764 50

Interaction of HIV with cultured human monocytes triggers not only cytokine production but also the release of natural cytokine inhibitors such as the soluble TNF receptors, levels of which are increased in the circulation of HIV-infected patients. We found that HIV-1 LAI induced the production by human monocytes from HIV-seronegative donors of another type cytokine inhibitor, the IL-1Ra receptor antagonist (IL-1Ra). HIV mainly induced the secreted form (83%) of IL-1Ra through de novo mRNA synthesis. IL-1Ra production was triggered at an early step of the infection process and involved the HIV envelope protein and the CD4 receptor. HIV-triggered IL-1Ra production occurred after a lag time, suggesting an indirect mechanism. Neutralizing Abs to IL-1 beta and IL-10 had no effect, while simultaneous treatment with anti-TNF-alpha, anti-granulocyte-macrophage CSF, and anti-TGF-beta nearly abrogated IL-1Ra release, supporting an indirect induction through the concerted action of the co-produced cytokines. IL-1Ra was induced by HIV in a mean 1,000-fold increase over IL-1 alpha beta, a ratio 20-fold higher than that obtained with LPS. This production masked 80% of IL-1 bioactivity in HIV-induced monocyte supernatants. These results suggest that the net balance between pro-inflammatory cytokines and their natural inhibitors could be critical in the control of the inflammatory process associated with HIV infection.
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PMID:HIV predominantly induces IL-1 receptor antagonist over IL-1 synthesis in human primary monocytes. 765 Apr 4

Using cocultures of human fetal brain cells and a chronically human immunodeficiency virus-1 (HIV-1)-infected promonocytic line U1, we investigated the effect of dynorphin, an endogenous opioid peptide found in the CNS, on upregulation of HIV-1 expression. Dynorphin and the synthetic kappa receptor agonist U50,488 promoted HIV-1 expression with a bell-shaped concentration-response relationship in which maximal effects were observed at 10(-13) and 10(-11) M, respectively. Pretreatment for 30 min with the kappa receptor antagonist nor-binaltorphimine completely blocked the stimulatory effect of dynorphin and U50,488. The involvement of cytokines on HIV-1 expression was tested. Dynorphin-induced upregulation of HIV-1 in the cocultures was largely blocked by antibodies to tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 but not by antibodies to IL-10. Also, dynorphin stimulated TNF-alpha and IL-6 in the brain cell cultures at both mRNA and protein levels, suggesting the involvement of these cytokines in opioid-induced HIV-1 expression. These findings suggest that endogenous opioid peptides such as dynorphin may have an immunomodulatory function in the CNS and could act as a cofactor in the neuropathogenesis of HIV-1.
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PMID:Upregulation of HIV-1 expression in cocultures of chronically infected promonocytes and human brain cells by dynorphin. 766 75

The present experiments were designed to study whether GTP binding protein activation and the resulting cAMP plays any role in HIV replication. The results showed that cholera toxin (CT) enhanced HIV replication dose dependently in myelo-monocytic cell lines latently infected with HIV-1, U1 and J22HL-60. Three- to 4-fold enhancement of virus production was observed in U1 cells and 4- to 11-fold enhancement in J22HL-60 cells 4 days after treatment with 100 ng/ml of CT. The increment of intracellular cAMP accumulation was parallel with HIV augmentation by CT in both cells. Even at the low concentration 0.1 ng/ml, TNF enhanced virus production to about an 80-fold higher level than the untreated U1 control cells as described previously (11). However, a synergistic effect (80- to 238-fold enhancement) was observed, when TNF-alpha and CT were added together to U1 cells. Similar synergism was seen in J22HL-60 cells. HIV antigen positive cells and gp120 expression were also increased to a similar degree. Phosphodiesterase inhibitor IBMX had no effect on HIV production alone, but potentiated HIV induction by CT and TNF. Adenylate cyclase activator, forskolin (FK), at 100 microM also significantly augmented HIV production (> 4-fold) and potentiated TNF induction in J22HL-60 and U1 cells. On the other hand, CT did not show any effect on HIV replication as well as TNF induction in HIV-1-infected T cell line. Northern blot experiment confirmed that this enhancement was mediated through the activation of HIV transcription. These data suggest that cAMP augments HIV replication and potentiates TNF induction in a particular monocyte-macrophage system.
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PMID:cAMP stimulates human immunodeficiency virus (HIV-1) from latently infected cells of monocyte-macrophage lineage: synergism with TNF-alpha. 768 59

Infection of CD4+ T cells by human immune deficiency virus-1 (HIV-1) causes severe dysfunction of cellular immunity, but paradoxically results in intense polyclonal activation of B cells, possibly accounting for both hypergammaglobulinaemia and frequent development of B-cell malignancies seen in HIV-infected patients. We have reported that human CD4+ T-cell clones infected with HIV in vitro markedly stimulate immunoglobulin synthesis by B cells through a non-cognate, contact-dependent mechanism. We show here that HIV-infected T-cell clones do not express the CD40 ligand (CD40L), a molecule critical for non-cognate B-cell activation, but a small proportion of them do express membrane tumour-necrosis factor (TNF)-alpha. The ability of HIV-infected T-cell clones to induce polyclonal B-cell activation appears to be restricted to TNF-alpha-positive T blasts and is inhibited by antibodies against both TNF-alpha and TNF-alpha receptor. Freshly isolated CD4+ T cells from HIV-infected individuals express TNF-alpha on the cell membrane and induce TNF-alpha-mediated immunoglobulin production by B cells. Thus, membrane TNF-alpha seems to be involved in the polyclonal B-cell activation induced by HIV-infected T cells.
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PMID:Membrane tumour necrosis factor-alpha is involved in the polyclonal B-cell activation induced by HIV-infected human T cells. 768 24

HIV infection is associated with abnormalities of cytokine production. A number of cytokines (IL-1, IL-6, TNF-alpha, interferons-alpha and -gamma) are produced at an increased level in vivo, whereas the production of IL-2 is decreased. This latter abnormality certainly plays an important role in the immunodeficiency of AIDS patients. Monokines (IL-1, IL-6, TNF-alpha) stimulate HIV replication in vitro, whereas the interferons decrease it. Cytokine effects on the in vivo spreading of HIV remain however to be determined. Cytokines may also be mediators of the clinical manifestations of AIDS. IL-1, IL-6 and TNF-alpha may induce tissue lesions of opportunistic infections and HIV encephalopathy. Cytokines, and mainly IL-6, may stimulate the growth of malignant cells in Kaposi sarcomas and in lymphomas. A better knowledge of the roles of cytokines in HIV infection may allow new therapeutic approaches using either recombinant cytokines or specific antagonists, with the aim of inhibiting both HIV spreading and the clinical manifestations of the infection.
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PMID:[Cytokines and AIDS]. 768 34

The initial infection with human immunodeficiency virus type 1 (HIV-1) in most individuals usually results in the establishment of a latent or chronic infection before eventual progression toward acquired immunodeficiency syndrome. HIV-1 can also establish a latent or persistent infection in some T cell lines that show minimal constitutive virus expression. However, activation of the T cell lines leading to enhanced HIV-1 replication can be induced by antigens, mitogens, and cytokines (tumor necrosis factor alpha [TNF-alpha], interleukin 1, and interleukin-2). Various gene products from other viruses (HTLV-1, HSV, EBV, CMV, HBV, and HHV-6) can also enhance HIV-1 long terminal repeat (LTR)-driven reporter gene activity. On the basis of these observations, it has been proposed that reactivation of latent HIV-1 harbored in chronically infected T lymphocytes, monocytes, or macrophages plays an important role in the pathogenesis of AIDS. So far, there are no drugs or therapy available that can provide protection against HIV-1 latency reactivation. ACH-2, derived from a human T cell line (CEM), is chronically infected with HIV-1, with low levels of constitutive virus expression. ACH-2 can be converted to productive infection by stimulation of the cells with 12-O-tetradecanoylphorbol-13-acetate (TPA), mitogen or cytokines (TNF-alpha), or infection with HSV. Therefore the ACH-2 cell line is a good candidate for studying the effects of drugs on HIV-1 activation. Previously, we have reported that DHEA and synthetic analogs of DHEA can be modest inhibitors of HIV-1 IIIB replication in phytohemagglutinin-stimulated peripheral blood lymphocyte cultures.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition of HIV-1 latency reactivation by dehydroepiandrosterone (DHEA) and an analog of DHEA. 769 6


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