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 retrovirus-induced murine AIDS (MAIDS) shares many features with human AIDS. Here, we examined the susceptibility of mice with MAIDS to staphylococcal enterotoxin-triggered shock. Following sensitization with D-galactosamine (D-Gal), mice with MAIDS were resistant to the otherwise lethal effect of superantigen staphylococcal enterotoxin A (SEA). Peak IL-2 levels in these mice after D-Gal/SEA challenge were 10-fold higher than those in uninfected controls, and concurrently, IL-10 levels rose markedly with reduction of circulating IL-1 and IFN-gamma. Treatment with neutralizing anti-IL-10 mAb before D-Gal/SEA challenge led to increased IFN-gamma levels in mice with MAIDS, and resulted in a dose-dependent mortality. In contrast, mice with MAIDS were more susceptible to the toxicity of bacterial endotoxin LPS than were uninfected controls. Administration of 100 micrograms LPS alone induced 50% lethality in mice infected with MAIDS virus 8 wk previously but not in uninfected controls. Administration of 10 micrograms LPS caused acute shock in D-Gal-sensitized mice with MAIDS. Peak TNF-alpha levels in these mice after LPS challenge were increased more than 10-fold, whereas IL-10 levels were one-third of those after SEA challenge. Moreover, serum IFN-gamma was undetectable in uninfected controls and rose to 1063 +/- 483 pg/ml in mice with MAIDS 4 h after LPS challenge. These results suggest that aberrant profiles of cytokine production are crucial in determining fatal outcome in these two types of septic shock in MAIDS.
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PMID:Lethal shock is inducible by lipopolysaccharide but not by superantigen in mice with retrovirus-induced immunodeficiency syndrome. 756 Oct 44

Cytokine expression was examined by reverse transcriptase-polymerase chain reaction (RT-PCR) in a retrospective sampling of 16 AIDS-associated large cell lymphomas (LCL). IL-6 receptor (IL-6R) and IL-10 expression was detected in a majority of the tumor specimens tested, IL-6 expression was detected in 5 of 16 lymphomas that also expressed IL-6R, suggestive of an autocrine mechanism of disease. A subset of tumor samples described as mixed immunophenotype contained large numbers of infiltrating T lymphocytes and macrophages. Immunoperoxidase staining of a representative tumor of mixed immunophenotype demonstrated the presence of HIV-infected macrophages that also stained with anti-IL-6. This finding suggests that IL-6 produced by nonlymphoid cells may act as a paracrine growth factor for tumor cells that express IL-6R. Although earlier studies of AIDs burkitt's lymphoma cell lines suggested that IL-10 expression required EBV infection, 7 of 12 AIDS LCLs that expressed IL-10 did so in the absence of EBV by EBER in situ hybridization. Because AIDS LCLs frequently express cell surface CD5, we speculate that IL-10 may act as an autocrine or paracrine growth factor for this class of lymphoma. These studies suggest that IL-6 and IL-10 are involved in the pathogenesis of AIDS-associated large cell and mixed immunophenotype lymphoma.
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PMID:Cytokine expression in large cell lymphoma associated with acquired immunodeficiency syndrome. 758 73

Female C57BL/6 mice were infected with LP-BM5 retrovirus, causing murine AIDS which is functionally similar to human AIDS. Dietary supplementation, with a 15-, 150- and 450-fold increase of vitamin E in a liquid diet, significantly restored levels of interleukin-2 (IL) and interferon-gamma produced by splenocytes, which were suppressed by retrovirus infection. Retrovirus infection elevated levels of IL-6 and IL-10 produced by splenocytes, which were significantly normalized by all levels of vitamin E supplementation, respectively. Increased levels of IL-6 and tumor necrosis factor-alpha, produced by splenocytes during progression to murine AIDS, were also significantly normalized by all levels of vitamin E supplementation. Vitamin E supplementation restored retrovirus-suppressed splenocyte proliferation and natural killer cell cytotoxicity. Vitamin E supplementation also alleviated the AIDS symptoms: splenomegaly and hypergammaglobulinemia. These data indicate that dietary vitamin E supplementation at extremely high levels was not immunotoxic, and can modulate cytokine release and normalize immune dysfunctions during progression to murine AIDS. It should favorably affect host resistance and thereby retard the development of AIDS.
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PMID:Modulation of immune function and cytokine production by various levels of vitamin E supplementation during murine AIDS. 762 53

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

Murine AIDS, induced by LP-BM5 murine leukemia retrovirus infection, causes a progressive and profound immunodeficiency in female C57B1/6 mice. Previously, we reported that autoantibodies were elevated during the initiation phases of this murine retrovirus infection and bound peptide determinants corresponding to CDR1 of several TCR V beta-chains. Therefore, we designed studies to determine whether administration of a major autoimmunogenic TCR V beta CDR1 peptide before or after infection with LP-BM5 retrovirus would modulate retrovirus-induced dysregulation of T cell function. Administration of the TCR V beta CDR1 peptide before murine retrovirus infection significantly prevented its suppression of splenic NK cell activity, T and B cell proliferation, and monokine (IL-6 and TNF-alpha) and Th1 cytokine (IL-2 and IFN-gamma) release by splenocytes, and inhibited retrovirus-induced elevation of Th2 cytokine (IL-5 and IL-10). Similar data were obtained with peptide immunization 2 wk after murine retrovirus infection at 6 and 16 wk postinfection. However, delaying peptide immunization until severe suppression of T and B cell mitogenesis had occurred did not restore their functions. Immunization with TCR V beta peptide prevents development of retrovirus-induced immune dysfunction, which suggests a possible pathogenic role of autoreactive T cells as regulatory elements.
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PMID:T cell receptor V beta complementarity-determining region 1 peptide administration moderates immune dysfunction and cytokine dysregulation induced by murine retrovirus infection. 763 74

Acquired immunodeficiency syndrome (AIDS)-related primary central nervous system lymphoma (PCNSL) is almost always associated with the Epstein-Barr virus (EBV), and EBV-DNA in cerebrospinal fluid (CSF) has been indicated as a useful tumour marker for this HIV-related neoplasm. AIDS lymphomas also show an enhanced production of IL-10 which is generally associated with the presence of EBV in lymphoma cells. We performed a prospective study in 19 HIV seropositive patients with brain mass lesions, and in 21 other AIDS patients with or without other neurological disorders, to assess the in vivo diagnostic value of EBV-DNA and of IL-10 levels in the CSF for primary lymphoma of the central nervous system (CNS). EBV-DNA was detected by a nested polymerase chain reaction (PCR) in the CSF from seven of eight patients with PCNSL, diagnosed by brain biopsy (87.5% sensitivity) and in none of the 11 controls with brain mass lesions (100% specificity) and of the other 21 AIDS patients with or without neurological disorders. The only patient with PCNSL without detectable EBV-DNA in the CSF was also negative for EBV-DNA in the lymphoma tissue, whereas the samples of the other seven brain lymphomas were all positive for EBV-DNA by nested PCR. Therefore 100% of patients with an EBV-positive primary CNS lymphoma had detectable EBV-DNA in the CSF. No patient from the control group without PCNSL with EBV-negative CSF developed a lymphoma after a mean follow-up of 157 +/- 173 d. IL-10 levels in the CSF from the patients with PCNSL were not significantly different from those in the other groups of patients with AIDS. Due to uniformly high levels in the CSF from AIDS patients, IL-10 is not a useful diagnostic marker for AIDS-related brain lymphoma. The detection of EBV-DNA from the CSF by nested PCR is an extremely sensitive and specific diagnostic tool for AIDS-related PCNSL and should be further evaluated as a possible alternative in patients from whom brain biopsy is not advisable.
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PMID:Evaluation of cerebrospinal fluid EBV-DNA and IL-10 as markers for in vivo diagnosis of AIDS-related primary central nervous system lymphoma. 766 63

The murine acquired immunodeficiency syndrome (MAIDS) caused by a defective murine leukemia virus produces severe immunodeficiency with abnormal lymphoproliferation and hypergammaglobulinemia. The presence of both CD4+ T cells and B cells is critical for the development of this disease. Remarkably elevated mRNA expression for IFN-gamma and IL-10 was observed in spleen cells of C57BL/6 mice starting from the early phase of viral infection. IFN-gamma production was induced by spleen cells from virus-infected mice upon stimulation with concanavalin A or lipopolysaccharide in both the early and late phases of MAIDS progression. When mice that had been passively administered anti-IFN-gamma mAb were infected with the virus, the development and progression of lymphadenopathy, immunodeficiency and elevated levels of serum IgG2a associated with MAIDS were delayed. Treatment with anti-IL-4 or anti-IL-10 mAb in place of anti-IFN-gamma mAb did not induce the delayed progression of MAIDS. These data support the concept that IFN-gamma-dependent pathway may be involved in the development of MAIDS.
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PMID:An IFN-gamma-dependent pathway plays a critical role in the pathogenesis of murine immunodeficiency syndrome induced by LP-BM5 murine leukemia virus. 769 11

Previous studies demonstrated that mucosal HIV p24 antigen content varied during the progression of HIV infection. In this study, expression of HIV RNA and mRNA of selected cytokines was examined in rectal mucosa from HIV-infected individuals. Rectal biopsies from 27 subjects were studied: 7 with CD4 counts > 500/mm3 (early), 11 with CD4 < 500 (intermediate), and 9 with AIDS (late), plus 4 HIV-seronegative controls. RNA in situ hybridization was performed using 35S-labeled riboprobes of HIV, TNF-alpha, IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-10, INF-alpha, IFN-gamma, and TGF-beta. HIV RNA was detected more frequently in the intermediate group than in the other groups (p < 0.005). Cytokine mRNA expression also varied during disease progression. The expression of IFN-alpha, IFN-gamma, and TGF-beta mRNA was most prevalent early in the disease; peak expression of IL-4, IL-5, IL-6, and IL-10 was seen during the intermediate stage, and peak expression of TNF-alpha and IL-1 beta mRNA were seen in AIDS patients. HIV RNA and cytokine mRNA expression vary during HIV disease progression. HIV RNA expression is greatest in the intermediate stage of the disease. The pattern of cytokine mRNA expression suggests predominant cell-mediated immunity under basal conditions and early in the disease, generalized cytokine activation in its middle phase, and proinflammatory cytokine activation in AIDS patients. Cytokine modulation of HIV expression in rectal mucosa in vivo may occur and have pathogenic importance.
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PMID:Variation in the expression of human immunodeficiency virus RNA and cytokine mRNA in rectal mucosa during the progression of infection. 770 12

Resistance to infection against a variety of pathogens requires the co-ordinated interaction of both the innate and acquired immune responses. Mice bearing the SCID mutation are devoid of T and B cells but retain elements of the innate immune system including natural killer (NK) cells, macrophages, granulocytes and complement proteins. Using the SCID model we have identified a T cell independent mechanism of macrophage activation mediated by the secretion of IFN-gamma from NK cells. This process occurs in response to a variety of parasites and bacteria including Listeria monocytogenes, and is strictly regulated both in vitro and in vivo by cytokines such as IL-2 and IL-10. Here we discuss the mechanisms of NK cell activation and regulation and describe a new model of opportunistic infection in SCID mice with the AIDS related pathogen Cryptosporidium parvum.
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PMID:Macrophage activation and innate resistance to infection in SCID mice. 771 56

This study was designed to determine if administration of anti-interleukin-4 (IL-4) monoclonal antibody (mAb), interferon-gamma (IFN-gamma) and their combination after LP-BM5 retrovirus infection of female C57BL/6 mice would prevent retrovirus-induction of immunosuppression and cytokine dysregulation. Splenic natural killer (NK) cell activity, T- and B-cell proliferation, and T-helper type 1 (Th1) and Th2 cytokine (IL-2, IFN-gamma, IL-5 and IL-10) and monokine [IL-6 and tumour necrosis factor-alpha (TNF-alpha)] secretions were monitored, as they are usually altered dramatically after murine retrovirus infection. Administration of IFN-gamma and anti-IL-4 significantly prevented retrovirus-induced suppression of splenic NK cell activity, and splenic T- and B-cell proliferation. They also significantly slowed retrovirus-induced elevation of Th2 cytokine (IL-5 and IL-10) release and monokine (IL-6 and TNF-alpha) secretion by splenocytes. They prevented the loss of Th1 cytokine (IL-2 and IFN-gamma) release by splenocytes, and alleviated splenomegaly and hypergammaglobulinemia, precursor signs of development of acquired immune deficiency syndrome (AIDS). These findings could provide insight into the roles of immunomodulator in AIDS treatment as well as the mechanisms by which retrovirus infection induces cytokine dysregulation, facilitating immunodeficiencies in AIDS.
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PMID:Anti-IL-4 monoclonal antibody and IFN-gamma administration retards development of immune dysfunction and cytokine dysregulation during murine AIDS. 783 63


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