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

Enhancement of immunity in the setting of HIV infection is difficult owing to loss of functional CD4+ T cells. The MHC class II-deficient mouse (II-/-) environment simulates that of the immunocompromised HIV-infected individual, since these mice have low CD4+ T cell numbers, defective CD4-dependent responses, and are susceptible to opportunistic infection. This strain was used to test whether heat-killed Brucella abortus (BA), covalently conjugated to the V3 peptide of HIV-1 (MN), could elicit anti-HIV responses. V3-BA, but not the T-dependent antigen V3-KLH, induced high levels of IL-12, IFN-gamma, and IL-10 mRNA in both wild-type (WT) and II-/- mice within 24 hr of injection. V3-BA-treated, but not V3-KLH-treated, II-/- mice developed serum IgG and IgA anti-V3 antibodies, with IgG2b and IgG3 as the predominant isotype. Viral neutralization studies, using a syncytium inhibition assay, demonstrated that the antibodies generated by V3-BA in II-/- mice were capable of neutralizing HIV. These experiments demonstrate that a heat-inactivated bacterium such as BA, when used as a carrier, can generate a cytokine environment that results in the production of neutralizing antiviral antibodies in an immunodeficient host. Such strategies could be important in the development of immunotherapies and vaccines for HIV-1 patients.
AIDS Res Hum Retroviruses 1998 Sep 20
PMID:HIV peptide conjugated to heat-killed bacteria promotes antiviral responses in immunodeficient mice. 976 10

The pathogenesis of AIDS-related non-Hodgkin's lymphomas (AIDS-NHL) involves accumulation of genetic lesions, stimulation and selection by antigen, as well as infection by viruses. Deregulation of cytokine loops has also been proposed to contribute to AIDS-NHL development, although data are available only for a limited number of cytokines. In this study we have utilized a panel of AIDS-NHL cell lines to investigate in detail the pattern of tumour expression and production of a wide spectrum of cytokines. The cytokines investigated included interleukin (IL)-1alpha, IL-1beta, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-13, TNF alpha, TNF beta, IFN gamma, TGF beta2, G-CSF, GM-CSF and SCF. The AIDS-NHL cell lines utilized were representative of both AIDS-related Burkitt lymphoma (AIDS-BL) and AIDS-related body cavity-based lymphoma (AIDS-BCBL). Overall, AIDS-NHL were found to produce IL-6, IL-10 and TNF beta, although with different patterns depending upon the biological features of the tumour. Production of high levels of IL10 preferentially associated with Epstein-Barr virus (EBV) positive AIDS-BL and AIDS-BCBL, although lower levels of the cytokine were also detectable among EBV-negative AIDS-BL. Production of IL-6 was restricted to EBV-positive AIDS-BL and AIDS-BCBL, whereas it was absent among EBV-negative AIDS-BL. Production of TNF beta clustered with AIDS-BL, whereas this was absent among AIDS-BCBL. These results define that the pattern of cytokine expression of AIDS-NHL depends upon the biological features of the tumour and may have implications for the pathogenesis of these disorders.
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PMID:Patterns of cytokine expression in AIDS-related non-Hodgkin's lymphoma. 979 1

Current data suggest that T-helper (Th)2-type cytokine responses are often associated with progression to AIDS in HIV-positive individuals. Similarly, Th2-type cytokines are associated with susceptibility to mucosal candidiasis, of which oropharyngeal candidiasis (OPC) is one of the most common opportunistic infections in HIV-positive individuals. Although little information is available on host defense mechanisms at the level of the oral mucosa, recent studies suggest that local cell-mediated immunity (CMI) is equally or more important than that in the periphery for host defense against mucosal Candida albicans infections. This study investigated the potential presence of oral-associated CMI through the expression of Th1/Th2-type cytokines in saliva of immunocompetent and immunocompromised individuals with and without OPC. Results showed a constitutive mixed Th1/Th2 cytokine expression (Th0) in whole saliva of healthy HIV-negative individuals. In contrast, HIV-positive individuals had a dominant Th2-type salivary cytokine profile (interleukin-4 [IL-4], IL-10) (IL-2, interferon-y [IFN-gamma], IL-12) that seemingly resulted from a lack of Th1-type cytokines rather than enhanced Th2-type cytokines. Moreover, pilot analyses of those with OPC showed evidence for a more profound salivary Th2-type profile. Both HIV-positive and HIV-negative patients, irrespective of CD4 counts, had some level of positive in vitro systemic lymphocyte proliferative responses to C albicans antigens. These results suggest that the Th1/Th2 cytokine dichotomy in HIV disease is detectable in situ in oral secretions and may be a useful indicator of oral-associated CMI to better understand resistance/susceptibility of HIV-positive individuals to oral opportunistic infections, including OPC.
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PMID:Th1/Th2 cytokine expression in saliva of HIV-positive and HIV-negative individuals: a pilot study in HIV-positive individuals with oropharyngeal candidiasis. 983 46

Marijuana, a widely abused drug in the US, and its derivatives (cannabinoids) have been used in AIDS and cancer patients for treatment of intractable nausea and cachexia. Yet, objective investigations of the effect of cannabinoids on the human immune system are few. We investigated the effect of delta9 tetrahydrocannabinol (THC) and cannabidiol (CBD) on cytokine production in vitro by human leukemic T, B, eosinophilic and CD8+ NK cell lines as models. THC decreased constitutive production of IL-8, MIP-1alpha, MIP-1beta, and RANTES and phorbol ester stimulated production of TNF-alpha, GM-CSF and IFN-gamma by NK cells. It inhibited MIP-1beta in HTLV-1 positive B-cells but tripled IL-8, MIP-1alpha and MIP-1beta in B-cells and MIP-1beta in eosinophilic cells but doubled IL-8. Both cannabinoids strongly inhibited IL-10 production by HUT-78 T-cells. Results indicate that THC and nonpsychotropic CBD have complex lineage and derivative specific effects on cytokines consistent with previous animal studies. These effects while of potential benefits in some inflammatory/autoimmune diseases may worsen HIV infection, tumorigenesis and allergic inflammation in the lung.
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PMID:Delta9 tetrahydrocannabinol and cannabidiol alter cytokine production by human immune cells. 985 61

The main factors in the pathogenesis of AIDS-dementia complex (ADC) are analyzed. The author suggests that these factors can be divided into two groups. The "nonspecific" factors present in every immunologic processes manifested by inflammation compose the first group. They are cytotoxic lymphocytes T, the immunoactivation of infected macrophages, cytokines, NO, NOS and iNOS, the increase of the BBB permeability, the accumulation of beta-amyloid precursor protein, excitotoxic amino acids, various and numerous cells adhesion molecules. The second group may contain factors connected with HIV-1 infection of CNS. In the pathogenesis of AIDS an important role is played by toxic glycoproteins gp 120 and gp 41 which are in the coat of HIV-1 virus, nucleotide sequences variability, possibility of various virus replication in various parts of CNS, the participation of lymphokines IL-4 and IL-10, and presence of co-receptors to HIV-1 virus on lymphocytes, macrophages, neurons and microglial cells.
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PMID:HIV-1-infection in the CNS. A pathogenesis of some neurological syndromes in the light of recent investigations. 1007 2

Toxoplasmosis has gained particular attention in the AIDS era as the most common opportunistic encephalitis in HIV-infected patients. Since there are important parallels between the human and rodent infection, experimental murine toxoplasmosis is widely used to study the immune reactions to this protozoal parasite. Oral application of low-virulent Toxoplasma (T.) gondii cysts leads to a biphasic disease characterized by an acute, generalized phase followed by a chronic stage confined to the brain, where an encephalitis with persistence of the parasite develops. Immunity to T. gondii is T cell mediated, and there is increasing evidence for a critical role of cytokines for an effective immune response. In order to address the functional role of interferon (IFN)-gamma in toxoplasmosis, we took advantage of mice lacking the IFN-gamma-receptor. Inactivation of the IFN-gamma-receptor rendered mice highly susceptible to T. gondii, and they died of a fulminant acute toxoplasmosis. Among the various organs affected, hepatitis was severe enough to cause death. In contrast to wild type animals, IFN-gamma-receptor-deficient mice were unable to activate their macrophages as evidenced by a lack of major histocompatibility complex (MHC) class II antigen induction and the absence of an upregulation of tumor necrosis factor (TNF)-alpha and inducible nitric oxide synthase (iNOS) mRNA transcripts, two macrophage effector molecules. These observations prompted the investigation of TNF- and TNF-receptor-mediated effects in toxoplasmosis by use of mice deficient in either the TNF-receptor type 1 (TNFR1) and/or the TNF-receptor type 2 (TNFR2). The lethal outcome of T. gondii-infected TNFR1/2- and TNFR1-deficient mice, but not of TNFR2-deficient and wild type animals, illustrated the important role of TNF-alpha and TNFR1-mediated signalling, respectively, in this infection. Histopathology attributed death of TNFR1- and TNFR1/2-deficient mice to a severe, necrotizing encephalitis. Unrestricted intracerebral parasite replication in these strains was associated with reduced numbers of iNOS+ leukocytes and a lack of iNOS mRNA induction in their brains as compared to resistant wild type and TNFR2-deficient mice. To precisely identify the cellular sources of cytokines in the brain, flow cytometry of leukocytes isolated from the brain, in situ hybridization, immunohistochemistry and RT-PCR analysis of cytokine mRNA transcripts of magnetically purified leukocyte populations were performed. These studies disclosed that both CD4+, CD8+ T lymphocytes and macrophages recruited to the brain as well as resident cell populations of the CNS including neurons, astrocytes and microglia contributed to the intracerebral cytokine synthesis. Each population was characterized by a specific cytokine pattern. Interestingly, activation of brain cells is a hallmark of Toxoplasma encephalitis. The marked induction of a variety of immunologically important cell surface molecules as MHC class I and II antigens, cell adhesion molecules and their ligands on microglia points to a particular important role of this cell type for the immune response to T. gondii, since the expression of these molecules is a prerequisite for cellular interactions with T cells. The observation of a prominent interleukin (IL)-10 production in the T. gondii-infected brain initiated studies addressing the function of this powerful immunosuppressive mediator in chronic Toxoplasma encephalitis. Neutralization experiments revealed that IL-10 facilitates persistence of the parasite in the brain by downregulating the intracerebral immune response. On the other hand, IL-10 may exert a regulatory role and may be necessary to prevent immunopathological effects of an uncontrolled immune response. In conclusion, these studies demonstrate the important role of the cytokines IFN-gamma and TNF-alpha and their receptors, respectively, for an effective control of T. gondii. In the CNS, the target organ of the parasite, a
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PMID:[Rudolf-Virchow Prize 1998. Award lecture. Toxoplasmosis: a model infection for studying systemic and intracerebral immune reactions]. 1009 13

To determine whether common skin diseases associated with human immunodeficiency virus (HIV) were distinguishable based on the pattern of serum cytokine expression, we studied patients with psoriasis, pruritus, and Kaposi's sarcoma (KS) for levels of tumor necrosis factor (TNF)-alpha, interferon-gamma (IFN-y), interleukin (IL)-10, and IL-4. Thirty-two HIV-positive (HIV+) patients including 8 with KS, 11 with psoriasis, and 13 with pruritus along with 16 HIV-negative subjects with psoriasis were studied. IFN-gamma levels were highest in sera of HIV+ patients with psoriasis (p = 0.040). By contrast, TNF-alpha and IL-10 levels were highest in sera of HIV+ patients with pruritus (p = 0.012). Detectable levels of all cytokines in these patients were remarkably higher than for healthy adults. These results suggest that common skin diseases associated with HIV infection and AIDS can be distinguished by the production of unique cytokines.
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PMID:Distinct serum cytokines in AIDS-related skin diseases. 1018 88

Dysfunction of cytotoxic activity of T and natural killer (NK) lymphocytes is a main immunological feature in patients with AIDS, but its basis are not well understood. It has been recently described that T and NK cell-mediated cytotoxicity can be regulated by HLA killer inhibitory receptors (KIR). In this work, we have determined on cytotoxic T cells and NK cells from HIV-1-infected individuals the expression of the following KIR molecules: p58, p70, and ILT2 (immunoglobulin-like family KIR) as well as CD94 and NKG2A (C-lectin-type family KIR). With some exceptions, no significant changes were found on the expression of immunoglobulin-like KIR in either CD8+ or CD56+ cells. Interestingly, the percentages of CD8+ and CD56+ cells expressing CD94 were significantly increased in these individuals. We also show that, in vitro, IL-10 up-regulates CD94 expression on CD8+ and CD56+ cells obtained from normal individuals, suggesting that the augmented expression observed in HIV-infected individuals could be related to the high levels of IL-10 previously described in HIV-1-infected individuals.
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PMID:Expression of killer inhibitory receptors on cytotoxic cells from HIV-1-infected individuals. 1019 20

Oxidative stress is suggested to be involved in several neurodegenerative diseases. One mechanism of oxidative damage is mediated by peroxynitrite, a neurotoxic reaction product of superoxide anion and nitric oxide. Expression of two cytokines and two key enzymes that are indicative of the presence of reactive oxygen intermediates and peroxynitrite was investigated in brain tissue of AIDS patients with and without AIDS dementia complex and HIV-seronegative controls. RNA expression of IL-1beta, IL-10, inducible nitric oxide synthase, and superoxide dismutase (SOD) was found to be significantly higher in demented compared with nondemented patients. Immunohistochemical analysis showed that SOD was expressed in CD68-positive microglial cells while inducible nitric oxide synthase was detected in glial fibrillary acidic protein (GFAP)-positive astrocytes and in equal amounts in microglial cells. Approximately 70% of the HIV p24-Ag-positive macrophages did express SOD, suggesting a direct HIV-induced intracellular event. HIV-1 infection of macrophages resulted in both increased superoxide anion production and elevated SOD mRNA levels, compared with uninfected macrophages. Finally, we show that nitrotyrosine, the footprint of peroxynitrite, was found more intense and frequent in brain sections of demented patients compared with nondemented patients. These results indicate that, as a result of simultaneous production of superoxide anion and nitric oxide, peroxynitrite may contribute to the neuropathogenesis of HIV-1 infection.
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PMID:Increased peroxynitrite activity in AIDS dementia complex: implications for the neuropathogenesis of HIV-1 infection. 1020 64

To examine the potential pathogenic role of IL-10 in HIV infection, we measured serum IL-10 levels in 51 HIV-infected patients and 23 healthy controls both on cross-sectional and longitudinal testing. All clinical groups (Centers for Disease Control (CDC) categories) of HIV-infected patients had significantly higher circulating IL-10 levels than controls, with the highest levels among the AIDS patients, particularly in patients with ongoing Mycobacterium avium complex (MAC) infection. Among 32 HIV-infected patients followed with longitudinal testing (median observation time 39 months), patients with disease progression had increasing IL-10 levels in serum, in contrast to non-progressing patients where levels were stable. While both IL-10 and tumour necrosis factor-alpha (TNF-alpha) increased in patients with disease progression, the IL-10/TNF-alpha ratio decreased in these patients, suggesting imbalance between these two cytokines. Finally, we found that highly active anti-retroviral therapy (HAART) induced a significant, gradual decrease in IL-10 levels but without normalization. These findings suggest a pathogenic role for IL-10 in HIV infection, and may suggest a possible role for immunomodulating therapy which down-regulates IL-10 activity in addition to concomitant potent anti-retroviral therapy in HIV-infected patients.
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PMID:IL-10 in HIV infection: increasing serum IL-10 levels with disease progression--down-regulatory effect of potent anti-retroviral therapy. 1020 14


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