UMLS:C0019693 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

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

Interleukin 10, a product of T and B cells and monocytes, displays many Th2-like properties through inhibition of Th1 cell functions. Interleukin 10 is thought to play a major role in the immune dysfunction seen in HIV-infected individuals. In this study, we evaluated in detail the production of IL-10 during HIV infection. Although the constitutive production of IL-10 did not differ in PBMCs from healthy donors and HIV-infected individuals, IL-10 was differentially produced in response to polyclonal activators. The overall plasma IL-10 levels were similar in 32 controls and 67 patients at different stages of the disease and receiving different antiretroviral drugs. However, patients with low CD4 T cell count (< 200/mm3) secreted approximately three-fold more IL-10 than did patients with high CD4 T cell count (> 500/mm3). Competitive/quantitative PCR revealed similar levels of mRNA expression in PBMCs from controls and HIV-infected individuals. In vitro HIV infection rapidly and transiently induced IL-10 production in PBMCs and monocytes, and the low level of endogenously secreted IL-10 failed to inhibit HIV replication in acutely infected monocytes. On the other hand, HIV infection of selected CD4+ T cell clones generated in a Th1- or Th2-like environment, differentially up-regulated IL-10 production, with significantly higher production by Th2 clones. Together, our data indicate that IL-10 production is more complex than previously thought, and may depend on several factors such as producer cells, nature of the stimuli, as well as viral isolates.
...
PMID:Differential production of interleukin 10 during human immunodeficiency virus infection. 884 18

The effect of exogenous recombinant interleukin 10 on the replication of low-passage HIV-1 strains in blood-derived monocytes and monocyte-derived-macrophages (MDMs) was examined at various stages of cell maturation after adherence to the plastic substrate. Interleukin 10 inhibited extracellular production of HIV-1 to a greater degree in monocytes infected within 24 hr of adherence than those infected at 5-7 days. Inhibition of viral production as extracellular p24 antigen was most marked when interleukin 10 was preincubated with monocytes for 24-96 hr (optimum, 48 hr), and increased between 2 and 100 ng/ml. Neutralizing antibody to IL-10 reversed the inhibition. Inhibition of HIV production from monocytes and macrophages was maximal at 1 week after a single addition of cytokine, but then HIV production rose to control levels. Interleukin 10 was also found to inhibit reversibly the normal increase in size and maturation of both uninfected and HIV-infected monocytes during 10-15 days of adherence. In addition, cytoplasmic and membrane expression of CD26, a marker of macrophage maturation, was markedly inhibited but the proportion of detaching, apoptotic, or necrotic cells was also not increased. Hence, interleukin 10 reversibly inhibits both monocyte maturation and HIV production from infected monocytes with similar kinetics, suggesting that inhibition of monocyte maturation by IL-10 may have a marked effect of HIV production by these cells.
...
PMID:The inhibition of HIV replication in monocytes by interleukin 10 is linked to inhibition of cell differentiation. 887 Aug 44

Correlates of progression of human immunodeficiency virus (HIV) infection to AIDS include the reduction in CD4+ T cells and the emergence of syncytium-inducing (SI) HIV variants. It has been suggested that progressive defects in interleukin 2 (IL-2), IL-12, and IFN- gamma production (type 1 cytokines), and increased production of IL-4 (and of IL-4-driven hyper-IgE), IL-6, and IL-10 (type 2 cytokines), could provide another correlate of disease progression. To determine the possible association among these markers, viral phenotype, cytokine production, IgE serum concentration, and rate of CD4 depletion were analyzed in a cohort of vertically HIV-infected children. We report that significantly higher production of type 2 cytokines and augmented IgE concentration are observed in children in whom HIV SI is isolated. In addition, we observed that the isolation of HIV SI and the production of high quantities of type 2 cytokines are correlated with increased loss of CD4 T cells in the 12 months preceding the determinations. These data suggest that the virologic and immunologic parameters characteristic of advanced HIV infection may be associated in pediatric HIV infection, and indicate a virologic-immunologic pathogenesis leading to the appearance of AIDS.
...
PMID:Virologic and immunologic markers of disease progression in pediatric HIV infection. 887 Aug 47

The aetiology of seborrhoeic dermatitis (SD) is still unknown. An increased number of Pityrosposurm ovale in lesional skin of patients with SD has been suggested to play a crucial role in the pathogenesis of the disease since double-blind trials with antifungal drugs (e.g. ketoconazole) have shown that these agents result in a significantly reduced disease intensity. The frequent association of HIV infection and SD may be due to a suppressed cell-mediated immunity. In order to characterize the role of the humoral and cellular immune response in patients with SD the effects of a P. ovale extract on the proliferation of, and interleukin-2 (IL-2), IL-10 by an interferon-gamma (IFN gamma) production, and immunoglobulin (IgA, IgG, IgM) synthesis by peripheral blood mononuclear cells (PBMC) from patients with SD were studied in vitro. Healthy volunteers served as controls. PBMC from normal donors responded with a significantly increased proliferation to P. ovale antigen, whereas cells from patients with SD did not. Additionally, IL-2 and IFN gamma production by PBMC from patients with SD was markedly depressed compared with normal cells after stimulation with P. ovale. However, stimulation of PBMC from SD patients with P. ovale antigen induced significantly increased IL-10 synthesis. IgA, IgG and IgM synthesis was significantly increased in cultures of PBMC from patients with SD whether the cells were antigen-stimulated or not. Our results support the assumption that strong skin colonization with P. ovale in SD is due to an altered cellular immunity, which may be induced by increased IL-10 secretion.
...
PMID:Effects of Pityrosporum ovale on proliferation, immunoglobulin (IgA, G, M) synthesis and cytokine (IL-2, IL-10, IFN gamma) production of peripheral blood mononuclear cells from patients with seborrhoeic dermatitis. 887 48

Modifications that we introduced into the implantation of human fetal thymus and liver into SCID mice (thy/liv-SCID-hu mice) markedly increased the population of human T cells and monocytes present in the peripheral blood and peripheral lymphoid compartment of these mice. As a result, the modified thy/liv-SCID-hu mice developed disseminated HIV infection after intraimplant or i.p. inoculation. After chronic HIV infection of these mice, depletion of the peripheral human T cells was observed as reported in HIV-infected individuals. In addition, these mice also developed plasma viremia after infection with HIV. The peripheral blood mononuclear cells were responsive to in-vivo cytokine regulation as evidenced by induction of human IFN-gamma gene expression by human IL-12 and inhibition by human IL-10. Acute treatment with human IL-10 but not with human IL-12 inhibited the development of plasma viremia and HIV infection in thy/liv-SCID-hu mice inoculated with HIV-1(59), a clinical isolate. SCID mice transplanted with cultured human fetal bone marrow displayed significant engraftment of the mouse bone marrow with human precursor cells and population of the peripheral blood with human B cells and monocytes. The peripheral blood of these bone marrow-transplanted SCID mice also became populated with human T cells after they were implanted with human thymic tissue due to migration of human precursor cells from the mouse bone marrow to the implanted human thymus. Thus, these modified SCID-hu mice should prove to be a valuable in-vivo model for studying the immunopathogenesis of HIV infection and for examining the in-vivo efficacy of immunomodulatory, drug and gene therapy in modifying HIV infection.
...
PMID:SCID-hu mice: a model for studying disseminated HIV infection. 888 45

Dendritic cells are potent stimulators of Ag-specific T cell responses and have been implicated in the pathogenesis of HIV-1 and other viral infections. Although cytokines may be involved in both of these processes, there is little information on the expression of cytokines by human blood dendritic cells. We characterized cytokine gene and protein expression in dendritic cells that were purified from normal human PBMC by flow cytometry and stimulated in vitro for up to 24 h with HIV-1 or herpes simplex virus (HSV). The unstimulated, uncultured dendritic cells were defined by their phenotype (HLA DR+ CD3- CD19- CD16- CD56- CD14-) and distinct morphology, lack of mRNA expression for CD3, CD14 and CD19, and presence of mRNA for CD4 and CD83. The purified dendritic cells also expressed CD4 (70-90%), CD33 (36-48%), and CD11c (44-54%); lacked CD1a expression (<1%); and were potent stimulators of an allogeneic MLR. The stimulated dendritic cells expressed mRNA for IFN-alpha, IL-1alpha, IL-1beta, IL-6, IL-10, IL-12, GM-CSF, and TNF-alpha within 4 to 12 h as determined by reverse transcription-PCR, with higher levels induced by HSV compared with HIV-1 strains IIIb or BaL. In contrast, the dendritic cells produced detectable protein only for IFN-alpha and IL-6 in response to HIV-1 or HSV, and IL-1beta in response to HSV within 24 h. There were no differences in expression of CD80 and CD86 surface molecules by dendritic cells that were either mock stimulated or stimulated with HIV-1 or HSV for 24 h. Production of IFN-alpha, IL-1beta, and IL-6 by dendritic cells may be important to the immunologic function of these cells and their role in the pathogenesis of HIV-1 and HSV infections.
...
PMID:Cytokine expression by human peripheral blood dendritic cells stimulated in vitro with HIV-1 and herpes simplex virus. 889 36

The state of activation of the immune system may be an important factor which renders a host more receptive to human immunodeficiency virus (HIV) and more vulnerable to its effects. To explore this issue with a practical in vivo model, we developed a modified protocol of HIV infection in hu-PBL-SCID mice. First, we assessed the time course of activation of human peripheral blood lymphocytes (hu-PBL) in the peritoneal cavity of SCID mice. At 2 to 24 h after the intraperitoneal injection into SCID mice, there was a clear-cut increase in the percentage of hu-PBL expressing early activation markers (CD69), concomitant with the release of soluble intercellular adhesion molecule-1 (sICAM-1) and the soluble interleukin-2 receptor (sIL-2R) and with the accumulation of mRNAs for a number of human cytokines. At 2 weeks, virtually all of the hu-PBL expressed the memory phenotype (CD45RO) and HLA-DR antigens as well. Cells collected from the SCID mouse peritoneum at 2 and 24 h after transplantation were fully susceptible to in vitro infection with HIV type 1 (HIV-1) in the absence of either IL-2 or mitogens. The injection of HIV into hu-PBL-SCID mice at 2 h after reconstitution resulted in a generalized and productive HIV infection of the xenochimeras. This early HIV-1 infection resulted in a dramatic depletion of human CD4+ cells and in decreased levels of sICAM-1 (in the peritoneal lavage fluid) as well as of sIL-2R and immunoglobulins M and A (in the serum). Enzyme-linked immunosorbent assay and/or reverse transcriptase PCR analysis showed higher levels of IL-4, IL-5, and IL-10 in the HIV-infected animals than in control hu-PBL-SCID mice, while gamma interferon levels in the two groups were comparable. When we compared the current model of HIV-1 infection at 2 weeks after the intraperitoneal injection of the hu-PBL in the SCID mice with the model described here, we found that the majority of immune dysfunctions induced in the 2-h infection of the xenochimeras are not inducible in the 2-week infection. This supports the concept that the state of activation of human cells at the moment of the in vivo infection with HIV-1 is a crucial factor in determining the immune derangement observed in AIDS patients. These results show that some immunological dysfunctions induced by HIV infection in AIDS patients can be mimicked in this xenochimeric model. Thus, the hu-PBL-SCID mouse model may be useful in exploring, in vivo, the relevance of hu-PBL activation and differentiation in HIV-1 infection and for testing therapeutic intervention directed towards either the virus or the immune system.
...
PMID:T-cell dysfunctions in hu-PBL-SCID mice infected with human immunodeficiency virus (HIV) shortly after reconstitution: in vivo effects of HIV on highly activated human immune cells. 889 19

Primary malignant lymphomatous effusions arising in individuals infected with the human immunodeficiency virus, type 1 (HIV-1) represent a rare subset of HIV-associated lymphomas. Previous studies have demonstrated that the malignant cells are monoclonal (as defined by rearrangement of the immunoglobulin gene), express cell surface CD38, and are infected with Epstein-Barr virus (EBV) and human herpes virus, type 8 (HHV-8). Despite these detailed molecular and immunophenotypic studies, clinical information on this disease entity is scant, prompting us to review the clinical features of eight cases seen at our institutions. All eight patients had total peripheral CD4+ lymphocytes < 200/microliter and presented with complaints related to body cavity distension. Routine laboratory values were nondiagnostic and yielded no prognostic information. Only two patients could tolerate and thus received chemotherapy with no obvious impact on their clinical course. The mean overall survival after diagnosis was 60 days (range 6-166 days). Four patients were examined at autopsy. The primary malignant lymphomatous effusion either was the immediate cause of death or contributed significantly to the death of only two. All four patients examined post mortem, however, had lymphomatous infiltration of serosal surfaces adjacent to the site of the primary malignant effusion. Molecular and immunologic studies performed on the malignant cells and effusion fluids revealed universal expression of cell surface CD38 and the presence of HHV-8 gene sequences, but in contrast with previous studies, only four had rearranged immunoglobulin genes or EBV present: IL-6 and IL-10 levels in the malignant effusion fluids were markedly elevated. In summary, this rare subset of HIV-associated lymphomas in our eight patients arose late in the course of HIV-associated disease, had a rapid clinical course, and was molecularly heterogeneous. A pathogenetic role for HHV-8 alone in this disease process is strengthened by our observation of four cases lacking EBV but containing HHV-8.
...
PMID:The natural history and molecular heterogeneity of HIV-associated primary malignant lymphomatous effusions. 889 66

We studied determinants of chronic inflammation and/or immune activation in plasma from patients in the transition from primary to early chronic HIV-1 infection. The following parameters were estimated in seven patients over time: plasma concentrations of soluble CD8 (sCD8), tumor necrosis factor alpha (TNF-alpha), soluble TNF receptor type II (sTNFRII), interleukin 6 (IL-6), soluble IL-6 receptor (sIL6R), IL-10, transforming growth factor beta1 (TGF-beta1), along with CD4- and CD8-positive T cell counts, p24 antigenemia, and clinical evaluation. Results showed that concentrations of sCD8, TNF-alpha, and sTNFRII, and peripheral CD8-positive lymphocyte counts, were significantly increased in patients, compared to HIV-negative controls, and showed a trend toward normal values over time. Levels of IL6, sIL6R, IL-10, and TGF-beta1 did not differ from those of controls and did not change over time. Heterogeneity was observed among the patients in terms of CD4-positive T cell depletion, levels of sCD8, concentrations of TNF-alpha/sTNFRII, and clinical outcome. These data indicate that in the transition phase from primary acute to chronic and asymptomatic infection the host immune activation in response to the virus is highly heterogeneous and that the sustained rise in TNF-alpha and its receptor may represent an important therapeutic target in early disease. The persistence of a state of chronic inflammation and/or immune activation could influence the progression of disease independently from CD4-positive T cell counts.
...
PMID:Cytokines and soluble receptor changes in the transition from primary to early chronic HIV type 1 infection. 890 93

T cell apoptosis has been proposed as an important contributor to the functional defects and depletion of T cells in HIV-infected individuals. However, the mechanisms involved in this apoptosis have not been elucidated. We recently showed that peripheral blood T cells from HIV-infected individuals are especially susceptible to Fas antigen-induced apoptosis. In this study we examine the role of Fas, CTLA-4, tumor necrosis factor (TNF) receptors (TNFR) and CD30, receptors known to be involved in T cell activation-induced cell death (AICD), in the spontaneous and activation (anti-CD3)-induced apoptosis of peripheral blood T cells from asymptomatic HIV-infected individuals. We report here that spontaneous and activation-induced T cell apoptosis cannot be inhibited by reagents that block interactions of Fas, CTLA-4, p55 and p75 TNFR and CD30 with their respective ligands. We also show that IL-12, IFN-gamma, IL-4 and IL-10 cannot modify spontaneous, activation- and anti-Fas-induced apoptosis. Anti-Fas preferentially induced CD4+ T cell apoptosis whereas AICD induced apoptosis equally in CD4+ and CD8+ T cells. We conclude that T cell AICD in HIV infection is not mediated by Fas, thus indicating that Fas-induced and activation-induced T cell apoptosis are independent mechanisms of apoptosis which may play different roles in the pathogenesis of HIV infection.
...
PMID:Activation-induced peripheral blood T cell apoptosis is Fas independent in HIV-infected individuals. 891

<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>