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

Cytokine production of unstimulated and mitogen-stimulated peripheral blood mononuclear cells of 31 children vertically infected with human immunodeficiency virus type 1 (HIV) and with different patterns of disease progression was evaluated to establish possible correlations between the immunologic and the clinical findings. Production of interferon gamma and interleukin-2 (type 1 cytokines), and of interleukin-4 and interleukin-10 (type 2 cytokines), was analyzed in seven symptom-free patients (Centers for Disease Control and Prevention class P-1B), 10 patients with mild symptoms (class P-2A), and 14 patients with severe symptoms (class P-2B-F). Cytokine production was compared with that of 10 age- and sex-matched control subjects who were seronegative for HIV. The HIV-infected patients produced significantly fewer type 1 cytokines and significantly more type 2 cytokines than the uninfected control subjects. No differences in the production of interferon gamma and interleukin-2 were detected among the different clinical categories of HIV-infected patients. In contrast, interleukin-4 production was augmented in the patients with class P-2A (p < 0.05) and class P-2B-F HIV infection (p < 0.03), in comparison with the children with class P-1B infection. The increase in interleukin-4 production was paralleled by an increase in the number of children with hyperimmunoglobulinemia E in each of the clinical groups (0% in class P-1B; 40% in class P-2A; and 71% in class P-2 B-F infection). Similarly, interleukin-10 production was increased both in patients with class P-2A and in those with class P-2B-F infection, in comparison with the children with class P-1B disease (p < 0.006 and < 0.04, respectively). These data indicate (1) that vertically acquired HIV infection results in decreased production of type 1 cytokines and in increased production of type 2 cytokines, and (2) that an increased production of type 2 cytokines correlates with hyperimmunoglobulinemia E and is present in, and may be characteristic of, the symptomatic phases of childhood HIV infection.
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PMID:Immunologic characterization of children vertically infected with human immunodeficiency virus, with slow or rapid disease progression. 786 94

Cytokine dysregulation in human immunodeficiency virus type 1 (HIV-1) infection has been documented in numerous studies and has been cited as an important component in the pathogenesis of this retroviral infection. Pharmacological modification of cytokine dysregulation, therefore, has been suggested as a therapeutic modality for HIV-1 infection. Dr. Dezube of Beth Israel Hospital (Boston) concisely reviews the state of our knowledge regarding the effects of pentoxifylline on expression of tumor necrosis factor-alpha, a cytokine known to influence HIV-1 replication and to play a possible role in the clinical manifestations of advanced infection with this virus. Pentoxifylline, a trisubstituted xanthine derivative, has been used to decrease blood viscosity and is reasonably well tolerated by most recipients of the drug. Results of preliminary studies, many of which were conducted by Dr. Dezube, suggest that use of this agent in combination with antiretroviral compounds may prove useful in the treatment of patients with HIV-1 infection.
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PMID:Pentoxifylline for the treatment of infection with human immunodeficiency virus. 791 14

Contribution of endothelial cells to normal immune processes (circulation of leukocytes, immune diapedesis, presentation of antigens) as well as to pathology caused by viral diseases is described. Cytokine secretion and expression of adhesion molecules, particularly during viral infections are described. Permissiveness of endothelial cells to HIV infection is presented. Contribution of herpesviruses (CMV, HSV) to thrombosis and atherosclerosis is also considered.
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PMID:[Contribution of endothelial cells to the immune processes. Influence of viral infections]. 797

Interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) have been implicated in the transition of nonreplicating latent human immunodeficiency virus (HIV) infection to the replicating state of productive infection. In HIV infection increased concentrations of these cytokines in serum have also been found in association with hypergammaglobulinemia. We have analyzed the ability of peripheral blood mononuclear cells (PBMC) of HIV-infected children to secrete IL-6 and TNF-alpha. In kinetic studies, optimum spontaneous IL-6 secretion by 1 x 10(6) PBMC was achieved at 24 hours. The mean spontaneous IL-6 and TNF-alpha concentrations secreted by PBMC of known HIV-infected children (age range, 8 months to 11 years) were 1686 and 131 pg/ml, respectively, compared with 56 and 45 pg/ml, respectively, in normal healthy controls. No significant correlation was observed between spontaneously secreted IL-6 and TNF-alpha in culture supernatants with CD4 or CD8 numbers; with serum IgG, IgA and IgM concentrations; or with lymphoproliferative responses to recall antigens. There was, however, an association between ability to secrete IL-6 with HIV-specific in vitro antibody production. Spontaneous IL-6 secretion decreased transiently after initiation of antiretroviral therapy, returning to original values with continued treatment. Cytokine derangement in HIV-infected children includes PBMC-derived spontaneous IL-6 and TNF-alpha secretion.
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PMID:Increased spontaneous secretion of interleukin 6 and tumor necrosis factor alpha by peripheral blood lymphocytes of human immunodeficiency virus-infected children. 807 36

Because HIV may alter the production of inflammatory factors produced by monocytes, the expression of tumor necrosis factor alpha (TNF-alpha), tissue factor (TF), interleukin (IL)-1 beta, and IL-6 was evaluated in 47 HIV-seropositive persons and seronegative control subjects. RNA was extracted from freshly isolated lipopolysaccharide (LPS)-stimulated or unstimulated monocytes. Cytokine and TF expression was quantitated by dot blot hybridization or a reverse transcription polymerase chain reaction (RT-PCR). A significant depression of TF mRNA was observed in LPS-stimulated monocytes (66% less in AIDS, 20% less in AIDS-related complex (ARC), and 0% less in asymptomatic patients), whereas normal responses were observed for TNF-alpha, IL-1 beta, and IL-6. When constitutive expression was measured in unstimulated monocytes by RT-PCR, a differential pattern was also observed. TNF-alpha and IL-1 beta were positive in 85% of asymptomatic persons, compared with only 27% of ARC and 42% of AIDS patients. Expression of IL-6 was observed in lower proportions, 27-30%, with no significant differences among disease states. All samples were negative for TF. Thus, the regulation of inflammatory molecules is differentially altered in individuals with HIV infection. TF is preferentially down-regulated, compared with TNF-alpha, IL-1 beta, and IL-6, in LPS-stimulated monocytes as patients progress to AIDS. TNF-alpha and IL-1 beta are preferentially up-regulated, compared with IL-6 and TF, in unstimulated monocytes in asymptomatic persons, with a loss of up-regulation as patients progress to AIDS.
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PMID:Dysregulation of cytokine expression in monocytes from HIV-positive individuals. 808 6

The reference treatment in visceral leishmaniasis is administration of antimonial compounds (Pentostam, Glucantime). Primary and secondary failures have been reported and may involve several mechanisms resulting in alterations in the T-cell-dependent response, particularly in HIV-positive patients. Alternative agents proposed for use as single-drug therapy or in combination with other drugs include Lomidine, which carries a high risk of toxicity, allopurinol, cytokines (IL-2 and interferon gamma), and amphotericin B. Amphotericin B, in addition to effects on the metabolism of sterols in the wall of the protozoan, induces macrophage activation. This article illustrates the difficulty of treatment of visceral leishmaniasis by reporting the case of an immunocompetent 36-year-old patient whose bone marrow cultures remained positive after successive treatment, over 48 months, with two courses of Glucantime (60 mg/kg/day for 15 days), one course of allopurinol (10 mg/kg/4 weeks), two courses of Glucantime in combination with interferon gamma, splenectomy, and one course of Pentostam (20 mg/kg/4 weeks). Bone marrow cultures became negative after administration of amphotericin B (1 mg/kg every 48 hours for 8 weeks). Cytokine studies disclosed defective production of IL-2, IL-1 beta, and IFN gamma. Amphotericin B seems to be a valuable alternative when conventional treatment fails. The liposomal form is especially promising.
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PMID:[Visceral leishmaniasis resistant to conventional treatments: value of amphotericin B]. 830 24

The mechanisms by which corticosteroids (CCs) improve the outcome of AIDS patients with severe Pneumocystis carinii pneumonia (PCP) are unclear. We studied IL1 beta and TNF alpha release from alveolar macrophages (AMs) of patients receiving CCs for the treatment of PCP and also the effect of in vitro hydrocortisone on this release. Cytokine release from AMs of AIDS patients with pulmonary complications not receiving CCs (group 1) was compared with that from AM of those receiving CCs for PCP (group 2). The AMs of HIV-negative normal subjects (group 3) served as controls. All participants were nonsmokers or exsmokers. We found that lipopolysaccharide-stimulated AM from group 2 released significantly less interleukin-1 beta (IL1 beta) and tumor necrosis factor alpha (TNF alpha) than AM from group 1 and was similar to that from group 3. There was a significant positive correlation between the amount of TNF alpha and IL1 beta released. The presence of HC in the culture medium reduced in vitro IL1 beta and TNF alpha release from stimulated AM of the three groups. Thus, stimulated AMs from AIDS patients who receive CCs for treatment of PCP release significantly less IL1 beta and TNF alpha than AM from patients not receiving CCs. These findings suggest a mechanism by which CCs improve the outcome of AIDS patients with PCP.
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PMID:Effect of corticosteroids on IL1 beta and TNF alpha release by alveolar macrophages from patients with AIDS and Pneumocystis carinii pneumonia. 836 85

Using human macrophage hybridomas infected with HIV-1, we investigated monocyte function over a 5-week period after HIV-1 infection. Two clones, 63 and 30, were infected with HIV-1IIIB. Infection was documented by RT activity (15 x 10(6) cpm/ml), intracytoplasmic staining with an anti-p24 antibody, in situ hybridization with an HIV-1-specific riboprobe, and electron microscopy showing intracytoplasmic virus. Two weeks after infection, clones 63 and 30 lost expression of all class II antigens (DR, 81.7 vs. 0%; DQ, 15.6 vs. 0%; and DP, 76.9 vs. 0%) while retaining expression of class I (87.4 vs. 84.1%), LFA-1 (82.4 vs. 83.1%), and LFA-3 (79.1 vs. 74.7%) antigens when compared to uninfected cells. When tested for functional integrity, infected but not uninfected clone 63 cells failed to stimulate a tetanus-specific MHC-restricted T cell proliferative response 2 weeks after infection. Cytokine secretion and antigen processing were also perturbed as production of IL-1 was abolished 2 weeks after infection (although IL-6 secretion was augmented) and infected clone 63 cells failed to process exogenous antigen. Last, the viability of T cells cocultured with infected clone 63 was dramatically decreased 35 days after infection (85 vs. 15%). There was no evidence of transmission of HIV-1 to T cells, suggesting a toxic effect of infected clone 63. Taken together, these data suggest that altered macrophage function in our system occurs at multiple levels, which may account for the early immunological defects described in HIV-1 infection.
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PMID:Progressive impairment of monocytic function in HIV-1-infected human macrophage hybridomas. 836 70

Hypersensitivity to trimethoprim-sulphamethoxazole (TMP-SMX) in patients with HIV infection may be a result of either immune dysregulation, a direct cytotoxicity of the SMX-hydroxylamine metabolite (SMX-HA) (rather than SMX per se), or glutathione deficiency. We evaluated the in vitro cytotoxicity of SMX and SMX-HA to peripheral blood mononuclear cells (PBMC) of HIV-infected subjects to determine if the degree of in vitro cytotoxicity is associated with hypersensitivity, whether glutathione inhibits cytotoxicity, and whether in vitro cytotoxicity is predictive for the development of hypersensitivity. Given that fever is often a prominent feature of hypersensitivity, we also assessed whether SMX or SMX-HA could induce the in vitro production of IL-1 beta, IL-6 or tumour necrosis factor-alpha (TNF-alpha) by PBMC. The cytotoxicities of SMX and SMX-HA to PBMC were assessed in 45 HIV-infected patients with prior TMP-SMX therapy, and in eight HIV- controls. Twelve HIV-infected subjects were studied prospectively before primary Pneumocystis carinii pneumonia (PCP) therapy or rechallenge with TMP-SMX in previously hypersensitive subjects. Cytokine production was measured in four hypersensitive and two non-hypersensitive HIV-infected subjects, and three HIV-uninfected controls. The cytotoxicity of SMX-HA to PBMC was significantly greater in the 22 HIV-infected patients with prior hypersensitivity than both the 23 HIV-infected patients without hypersensitivity and the control group. Cytotoxicity was significantly reduced by glutathione only in the hypersensitive group. SMX did not induce cytotoxicity in any group. In 12 subjects studied prospectively, SMX-HA cytotoxicity was also significantly greater in those with subsequent hypersensitivity. Exposure of PBMC to SMX-HA resulted in a modest increase in the production of IL-6, IL-1 beta and TNF-alpha, although no major difference was detected between subjects with or without hypersensitivity. These data suggest that SMX-HA and glutathione deficiency are involved in the pathogenesis of hypersensitivity to TMP-SMX in HIV-infected patients, and that in vitro cytotoxicity could be useful in the diagnosis of hypersensitivity and predicting its likelihood.
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PMID:In vitro cytotoxicity as a marker of hypersensitivity to sulphamethoxazole in patients with HIV. 840 9

Because cytokines have a central role in the regulation and function of the human immune system, expression of several key cytokine genes in HIV infection was compared by quantitative polymerase chain reaction studies in lymphocytes from HIV-seronegative and -seropositive subjects. Elevated levels of IFN-gamma mRNA and lowered IL-2 mRNA were found in the PBMC of eight seropositive men with CD4 T cells over 500/mm3 (mean, 647/mm3), whereas IL-4 and IL-10 mRNA were not changed significantly. PBMC obtained 2 yr later from four of these patients with stable disease status (unchanged CD4 T cell number) showed median mRNA levels that were nearer normal for IFN-gamma and for IL-2. Four other men whose CD4 levels fell more than 200/mm3 in the following 2 yr, however, showed increased IFN-gamma and lowered IL-2. Purified CD4 and CD8 T cells from 10 HIV-seropositive and 10 -seronegative homosexual men were compared. Cytokine gene expression was found to be markedly different in CD4 and CD8 T cells from HIV-seropositive men. In CD8 T cells on a per-cell basis, the levels of cytokine mRNA were substantially lower than in CD4 T cells and were not markedly changed in HIV infection. In the CD4 T cells, on a per-cell basis, the mean mRNA levels of IFN-gamma, IL-10, and TNF-alpha were increased substantially (p < 0.001) in HIV infection. IL-2 gene expression was not increased significantly. Thus, the low IL-2 mRNA expression seen in PBMC is primarily due to the reduced CD4 T cell numbers. Increased expression of IFN-gamma genes in CD4 T cells, however, indicates that these cells may be responsible for substantial amounts of circulating IFN-gamma that occur in HIV infection. The striking difference in the effect of HIV infection on the expression of IFN-gamma and IL-2 genes indicates that these cytokines are under separate control. IL-4 mRNA levels were not changed. IL-10 gene expression, however, was increased more in early HIV infection, with less of an increase later. Expression of all cytokines in CD4 T cells appeared to subside late in HIV infection. However, the balance of cytokine expression was altered in all stages of HIV infection.
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PMID:Elevated IFN-gamma and decreased IL-2 gene expression are associated with HIV infection. 840 54


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