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

Disturbances of interferon synthesis with the hyperproduction of unusual kinds of interferons may be the initial step which triggers autoimmune disease through a concatenation of pathological reactions including the disturbance of several immunological and interferon cascades. This fundamental disturbance can result either from a genetic predisposition or from the influence of certain viruses (or viral particles) or both factors together. The administration of interferons to individuals with an underlying or latent autoimmune condition can exacerbate or trigger the disease. AIDS has many features similar to autoimmune disease, including the hyperproduction of aberrant interferon, a type with little or no anti-HIV activity, protectively induced by HIV to allow its continued replication and survival. In other words, while most viruses induce normal IFN which protects the cells against viral infection, HIV induces an abnormal, defective kind of IFN which insures viral survival. The neutralization of hyperproduced interferons by polyclonal or monoclonal antibody produced in mouse, or preferably, human hybridoma, removal via extracorporeal means, or the use of antagonists which diminish the production or biological activity of these interferons can be a therapeutic approach to the management of these chronic diseases. In addition, the extracorporeal removal of different kinds of interferons, autoantibodies, autoantigens and other substances from the organism in certain pathological conditions may be an effective and safe method of treatment for autoimmune diseases and AIDS.
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PMID:A disturbance of interferon synthesis with the hyperproduction of unusual kinds of interferon can trigger autoimmune disease and play a pathogenetic role in AIDS: the removal of these interferons can be therapeutic. 769 57

We previously reported that human immunodeficiency virus type 1 (HIV-1), herpes simplex virus (HSV), and Sendai virus induce higher levels of alpha interferon (IFN-alpha) in blood dendritic cells than in monocytes of healthy donors. In the present study, the levels of IFN-alpha induced by T-cell tropic (IIIb and RF) and monocytotropic (BaL) strains of HIV-1 and by HSV were significantly decreased in peripheral blood mononuclear cells (PBMCs) derived from subjects with asymptomatic and symptomatic HIV-1 infection. In contrast, Sendai virus, a paramyxovirus that induces proportionally more IFN-alpha in monocytes and B cells than do either HIV-1 or HSV, stimulated normal levels of IFN-alpha in PBMCs from the HIV-1-infected men. The IFN-alpha produced by PBMCs from the HIV-1-seropositive subjects was partially acid labile, whereas the IFN-alpha produced by PBMCs from the HIV-1-seronegative donors was acid stable. We hypothesize that there is a selective defect in IFN-alpha production by peripheral blood dendritic cells, whereas the host retains the IFN-alpha-producing capacity of monocytes and B lymphocytes. The loss of IFN-alpha production in response to HIV-1, herpesviruses, and possibly other pathogens could contribute to the progression of HIV-1 infection and to the development of AIDS.
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PMID:Selective decrease in human immunodeficiency virus type 1 (HIV-1)-induced alpha interferon production by peripheral blood mononuclear cells during HIV-1 infection. 769 20

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

Inflammatory cells in lymph nodes of eighteen patients suffering from culture-proven tuberculous lymphadenitis were examined by histological and immunohistochemical techniques. Ten patients suffered from symptomatic HIV-infection and eight patients were immunocompetent individuals without HIV-1 serology. Characteristic granulomas with or without caseation were observed in eight immunocompetent and four HIV-1-infected patients with less marked lymphopenia of CD4 positive peripheral blood lymphocytes. No epitheloid cell formation was present in lymph nodes of HIV1-infected patients with more severe depression of CD4 positive peripheral blood lymphocyte count. Foamy macrophages were found instead of these cells. While many cells--predominantly lymphocytes--express CD25 (IL-2 receptor) in cases with typical epitheloid granulomas there is no such CD25 expression in cases without any epitheloid cell formation. This result suggest that T cell function is necessary for epitheloid granuloma formation in human tuberculosis. The phenotype of macrophages underwent progressive changes parallel to decreasing numbers of CD4 positive peripheral blood lymphocytes. Foamy macrophages in Mycobacterium avium-intracellulare infection represented an end-stage phenotype. They were positive for S100 protein and they did not express lysozyme, alpha-1-anti-chymotrypsin, L1 antigen (Mac387) and CD4, whereas positivity for HLA-DR, CD68 and Ki-M8 was preserved. In situ immunohistochemical demonstration of IFN-alpha, IFN-beta, TNF-alpha, IL-1 and IL-6 revealed that foamy cells in M. tuberculosis infection were highly active effector cells. They contained higher concentrations of the examined cytokines than epitheloid cells in the lesions of HIV+ and HIV-patients. Corresponding to these findings the histological proof of acid-fast bacilli was generally not successful in typical HIV-associated tuberculosis. The foamy appearance may result from the lipid-rich cell membranes of destroyed acid-fast bacilli. In contrast acid-fast bacilli-packed foamy macrophages in AIDS patients with M. avium-intracellulare (MAI) infection did not produce any of the examined cytokines.
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PMID:Immunohistochemical analysis of cell composition and in situ cytokine expression in HIV- and non-HIV-associated tuberculous lymphadenitis. 771 49

The anti-Friend leukemia virus (FLV) effects of interferon-alpha-A/D (IFN-alpha) and 2',3'-didehydro-2',3'-dideoxythymidine (stavudine) used alone and in combination were examined in Mus dunni cells using a checkerboard-type experiment design. Strong antiviral synergy and a suggested cytotoxic synergy were seen. In two experiments to evaluate the effect of combining therapy with IFN-alpha and stavudine against FLV disease in the hybrid mouse strain (B10.A x A.By)F1, which is a strong producer of cytotoxic T cells, the drug combination resulted in better inhibition of FLV disease than did either drug used alone. Combination therapy inhibited splenomegaly, splenic virus infectious centers, plasma virus, and the virus-induced increase in hematocrit to a greater degree than did either drug alone. These data indicate that combination therapy with stavudine and IFN-alpha is effective in the treatment of murine retrovirus infections and may be of value in the treatment of human AIDS.
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PMID:Effect of the combination of interferon-alpha and stavudine on Friend virus infections in (B10.A x A.By)F1 mice. 786 Oct 24

AIDS is associated with three major neurological syndromes: dementia (HIVD), vacuolar myelopathy (VM) and plainful sensory neuropathy (PSN). The pathogenesis of these conditions remains unclear although they all demonstrate a marked increase in macrophage number and activation despite systemic immunosuppression. It was therefore of interest to determine the profile of cytokine and HIV expression in brain, spinal cord and peripheral nerves of AIDS patients with AD, VM and PSN, as compared to AIDS patients without neurological disease and seronegative controls. RNA was extracted from brain, spinal cord and peripheral nerve and RT/PCR for cytokine and HIV mRNA was performed. In situ RT/PCR was performed to determine the number and type of cells expressing cytokine message and this was compared to the number of cells containing HIV DNA detected with in situ PCR. We found a consistent profile of increased TNF alpha and decreased IFN gamma and IL4 in all three syndromes compared to AIDS patients without neurological disease. IL1 did not increase in parallel with TNF alpha IL10 was decreased in the VM tissue. HIV transcripts were increased in the AD brains compared to non-demented controls but were detected only occasionally in spinal cord and not at all in peripheral nerve. Preliminary data from in situ RT/PCR suggests that a large number of cells are expressing. TNF alpha but only a small number are infected with HIV.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cytokine dysregulation in HIV-associated neurological disease. 787 88

Similarly to HIV-infected cells, recombinant HIV-1 glycoprotein 120 induces acid-labile interferon production in peripheral blood mononuclear cells from healthy donors. Acid lability of this interferon is due to the presence of both IFN-alpha and -gamma molecules. In fact, although not revealed by neutralization of antiviral activity with antibody to IFN-gamma, the presence of IFN-gamma was shown both immunoenzymatically and by detection of specific mRNA in gp120-stimulated cells. The source of IFN-gamma appears to be a T cell present in the CD4-enriched subpopulation. Cultures treated with monoclonal antibodies to the ICAM-1 and LFA-1 adhesion molecules showed an impaired release of both IFN types after gp120 stimulation, suggesting a crucial role of cell-to-cell interactions in the process leading to IFN production. Our data suggest that the HIV envelope glycoprotein could be responsible for the induction of endogenous IFN-alpha and -gamma observed in AIDS patients.
AIDS Res Hum Retroviruses 1993 Oct
PMID:Coordinate induction of interferon alpha and gamma by recombinant HIV-1 glycoprotein 120. 790 70

HIV-induced cytokine dysregulation, including overproduction of the antiproliferative and cytolytic IFN alpha cytokine, represents a major component of the immune disorders characterizing AIDS. To block the overproduction of IFN alpha we designed an AIDS vaccine combination which included both an anti-HIV and/or an anti-IFN alpha immunization. The safety and immunogenicity of this multicomponent vaccine were tested in mice, Cercopithecus, two HIV noninfected individuals, and six HIV-1 seropositive immunocompromised patients enrolled in a 1-year open clinical trial. We now report the result of a 9-month short-term randomized, blind, placebo-controlled clinical trial (Phase I/II) performed in HIV-1 patients (22 individuals) to confirm safety/tolerance of the anti-IFN alpha vaccine and its immunogenicity and to evaluate whether the complex vaccine initially used could be simplified by removal of HIV component(s). Three groups of patients received inactivated IFN alpha (i-IFN alpha) associated with the immunomodulator P40 with HIV-1 antigens (groups B and C) or without (group A), and one group (D) was placebo. The clinical follow-up documented among those receiving i-IFN-alpha showed that none developed AIDS and/or required antiretroviral chemotherapy. Viral load did not increase and CD4 cell count as well as cell-mediated immunity (CMI) stabilized or even significantly increased in group A. Immunogenicity of the preparations was determined by a positive delayed-type hypersensitivity (DTH) reaction to i-IFN alpha and the presence of serum antibodies to i-IFN alpha and to HIV-1 peptides, occurring only in treated patients. As previously planned, based on these safety data, the trial has been extended for an additional year and all patients were switched to protocol A (i-IFN alpha+P40). This second period of the trial, now open and ongoing, should allow us to evaluate further the innocuity of the i-IFN alpha preparation and whether anti-IFN alpha vaccine could provide a long-lasting CD4 cell count as well as CMI stabilization.
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PMID:A randomized, placebo-controlled, blind anti-AIDS clinical trial: safety and immunogenicity of a specific anti-IFN alpha immunization. 791 35

Four cardinal immune disorders interacting with each other may promote the progressive T cell depletion and immunosuppression characterizing AIDS. Immune activation of HIV-1 infected T4 cells leads to virus release and premature cell death. Both virus release with its resulting viral load and dead cells are the source of gp120 stimulus. Anergy of non-infected CD4 cells, resulting in cytokine dysregulation may be promoted by impairing the CD4-MHC interaction during CD4 cell activation either directly through the SLWDQ pentapeptide identity with the CD4 molecule and the CD4 binding region or through a gp120-induced autoimmune reaction to CD4. Overproduction of IFN alpha, the known antiproliferative and cytolytic cytokine may promote in a paracrine manner to neighbouring cells the immunosuppression generated by the lack of IL2 secretion following CD4 cell anergy. Apoptosis of activated non infected T cells could be induced by effector components of the autoimmune reaction (CTL, Lymphotoxins or Abs?) directed towards the 2 consensus gp120 sequence identity/similarity (INCTR and FYCNST) shared with the APO/Fas molecule. These two sequences are known as immunodominant sites of the gp120. Furthermore, IFN alpha overproduction may also render circulating memory T cells competent to apoptosis by upregulating the cascade of metabolic events leading to programmed cell death.
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PMID:Pathogenic disorders involved in immunosuppression and T cell depletion characterizing AIDS. 791 98

Since the immune system is impaired in the course of HIV-infection, the purpose of any AIDS vaccine therapy should be the restoration in the patient of an adequate immunocompetence to enable him to respond to the antigenic stimulus represented by the virus. In the present investigation we have shown the antiproliferative action on activated T-cells in culture of: sera taken from HIV-infected, but not seronegative individuals; T lymphocytes taken from seronegative subjects and infected in vitro with HIV but not non infected cells; native alpha-IFN and the time-dependent inactivation of this activity by formaldehyde treatment of alpha-IFN. Thus is confirmed the major contribution provided by alpha-IFN to the immunosuppression occurring in the course of HIV-infection. These results also strongly support the new AIDS vaccine therapy strategy based on the administration to HIV-infected patients of inactivated, but still immunogenic alpha-IFN. To the alpha-IFN treatment could also be combined the administration of fixed autologous suppressive cells. The induction of gamma-IFN in addition to alpha-IFN production by stimulation of cells from healthy donors with gp120 should encourage the use of a vaccine combining both inactivated alpha-IFN and gamma-IFN. On the other hand, the IL-12 cytokine with its potential to restore compromised cell-mediated functions associated with HIV infection should also be a valuable adjuvant treatment.
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PMID:Involvement of alpha-interferon in HIV-1 induced immunosuppression. A potential target for AIDS prophylaxis and treatment. 791 8


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