Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human immunodeficiency virus (HIV) infection is the primary cause of morbidity and mortality in Malawi, Africa, because of its many effects on the immune system. Immune cells communicate through cytokines; therefore, we examined the relationships between HIV serostatus and cell-specific cytokine production for 40 asymptomatic, employed adults and 312 acutely ill, hospitalized patients in Malawi. We also measured the plasma HIV-1 RNA levels of 13 asymptomatic persons and 83 patients found to be HIV(+). We incubated peripheral whole blood with brefeldin-A +/- phorbol 12-myristate 13-acetate and ionomycin and then permeabilized, fixed, fluorescently stained, and examined the mononuclear cells with four-color, six-parameter flow cytometry. The percentage of lymphocytes expressing CD4 did not differ significantly between the HIV(+) and HIV(-) healthy adults (medians, 35.2 vs. 40.8%, respectively), but a wide array of cytokine parameters were lower in the HIV(+) than in the HIV(-) asymptomatic persons, for example, median percentages of T cells producing induced interleukin 2 (IL-2) (8.7 vs. 16.5%, respectively) and spontaneously producing IL-6 (0.7 vs. 11.0%, respectively). Also, four T cell parameters reflecting type 2-to-type 1 cytokine balances (T2/T1) were higher in the HIV(+), versus HIV(-), asymptomatic persons. Unlike the healthy adults, for patients with mycobacteremia/fungemia or malaria, the HIV(+) patients had higher median percentages of T cells and CD8(+) T cells producing induced interferon gamma than did the HIV(-) PATIENTS: For both asymptomatic and acutely ill persons, HIV-1 plasma levels were positively correlated with T2/T1 parameters. Cell-specific cytokine effects of HIV infection may precede measurable effects on CD4 expression. Cytokine therapies, even beyond periodic administration of IL-2, may improve the responses of HIV-infected persons to both HIV and coinfections.
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PMID:Peripheral blood cell-specific cytokines in persons with untreated HIV infection in Malawi, Africa. 1248 8

We have proposed a unifying hypothesis of the etiopathogenesis of autoimmunity that defines autoimmunity as a type I interferon (IFN) immunodeficiency syndrome. We have examined toxicity and potential efficacy in three phase I (type 1 diabetes, rheumatoid arthritis, multiple sclerosis) and one phase II clinical trials in multiple sclerosis (MS). In a phase I open-label trial in type 1 diabetes, ingested IFN-alpha preserved residual beta cell function in recent onset patients. In a second phase I trial, treatment of rheumatoid arthritis (RA) with ingested IFN-alpha reduced the secretion of interleukin-1 (IL-1), a proinflammatory cytokine. In a third phase I trial in MS, there was a significant decrease in peripheral blood mononuclear cell (PBMC) IL-2 and IFN-gamma production after ingesting IFN-alpha. In a phase II randomized, placebo-controlled, double-blind trial in MS, 10,000 IU ingested IFN-alpha significantly decreased gadolinium enhancements compared with the placebo group at month 5. Tumor necrosis factor-alpha (TNF-alpha) and IFN-gamma cytokine secretion in the 10,000 IU group at month 5 showed a significant decrease that corresponded with the effect of ingested IFN-alpha on decreasing gadolinium enhancements. Ingested IFN-alpha was not toxic in any of these clinical trials. These studies suggest that ingested IFN-alpha may have a potential role in the treatment of autoimmunity.
J Interferon Cytokine Res 2002 Dec
PMID:Ingested type I interferon: a potential treatment for autoimmunity. 1258 87

Most cases of human immunodeficiency virus (HIV) infection worldwide occur following sexual contact, implying that the virus may breach the protective epithelial barrier lining the genital tract. HIV infection is known to preferentially occur when the genital epithelial integrity is altered, particularly when epithelial micro-ulcerations occur during heterosexual intercourse or ulcerations appear, due to sexually transmitted infections or else in the context of ectopy of the endocervical mucosa, which may leave the genital tissue. We report that R5-tropic infectious HIV-1 isolates are capable of in vitro transcytosis through a tight and polarized monolayer of human endometrial HEC-1 cells. Transcytosis of HIV particles was increased 2-fold within a pro-inflammatory micro-environment. Our findings suggest that transcytosis may be a relevant mechanism for the passage of virus through the genital mucosa in vivo, particularly when inflammatory cells and mediators are present in the vicinity of the mucosal surface.
Cytokine 2002 Dec 21
PMID:Enhanced transcytosis of R5-tropic human immunodeficiency virus across tight monolayer of polarized human endometrial cells under pro-inflammatory conditions. 1263 71

Murine lupus can occur spontaneously or be induced by hydrocarbons, such as pristane. Spontaneous disease in MRL and NZB/W F1 mice is suppressed by the xid (X-linked immunodeficiency) mutation, which greatly diminishes T cell-independent type 2 responses as well as the number of peritoneal B1 cells. The present study asked whether lupus induced by i.p. injection of pristane likewise is inhibited by the xid defect. Male CBA/N (xid) mice were refractory to the induction of autoantibodies by pristane, whereas 23% of pristane-treated male CBA/CaJ controls produced anti-nRNP/Sm, -Su and/or -OJ (isoleucyl tRNA synthetase) antibodies. Unexpectedly, 43% (12 of 28) of the xid mice spontaneously produced anti-nuclear antibodies that proved highly specific for the lupus antigen RNA helicase A (RHA). Strikingly, this specificity was absent in CBA/CaJ mice (none of 51). Moreover, pristane treatment suppressed the production of anti-RHA antibodies when administered prior to the onset of autoantibody production, but enhanced anti-RHA levels when given after the onset of autoantibody production, suggesting that pristane interferes with anti-RHA production at an early stage. Large amounts of IgG1 anti-RHA autoantibodies were detected in the sera of xid mice, whereas pristane-induced anti-nRNP/Sm and -Su autoantibodies were almost exclusively IgG2a. Cytokine production within the peritoneal cavity reflected the predominant isotypes: IL-12 and IFN-gamma predominated in pristane-treated mice, whereas IL-4 and IL-6 were more predominant in untreated xid mice. The spontaneous production of anti-RHA by xid mice and its suppression by pristane treatment at the level of autoantibody induction supports the idea that lupus autoantibodies may be generated through a variety of mechanisms.
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PMID:X-linked immunodeficient mice spontaneously produce lupus-related anti-RNA helicase A autoantibodies, but are resistant to pristane-induced lupus. 1291 64

In human immunodeficiency virus type 1 (HIV-1)-infected individuals, virus-induced production of interferon alpha (IFN-alpha) is impaired. In order to obtain regulated expression of IFN-alpha that responds to HIV-1 infection, a recombinant SV40 vector was designed that carries the human IFN-alpha2 cDNA under the control of the HIV-1 long terminal repeat (LTR) (SV[HIVLTR]IFN). Thus, the IFN-alpha2 gene would be trans-activated on infection with HIV-1. This vector was tested to determine if central nervous system (CNS) cell types that may be potential HIV-1 targets could be transduced and protected from HIV. SV[HIVLTR]IFN transduced NT2 cells, a human neuronal precursor cell line, mature neurons derived from NT2 precursor cells, and human primary monocyte-derived macrophages. IFN-alpha2 expression was retained in mature neurons after SV[HIVLTR]IFN-transduced NT2 precursor cells were induced to differentiate using retinoic acid. IFN-alpha expression was detected only after exposing transduced cells to HIV. Furthermore, SV[HIVLTR]IFN-delivered IFN-alpha2 expression significantly inhibited replication of multiple strains of HIV in both NT2 and NT2-derived mature neurons. SV[HIVLTR]IFN transduction also inhibited HIV-1(BaL) replication in human primary monocyte-derived macrophages. Therefore, we have demonstrated the effectiveness of IFN-alpha2, delivered by an SV40 vector driven by HIV-1 LTR as a promoter, to protect several CNS-based, potentially HIV-susceptible cell types. These findings may have implications for therapy of HIV-1 infection in the CNS.
J Interferon Cytokine Res 2003 Sep
PMID:Inhibition of HIV-1 in the central nervous system by IFN-alpha2 delivered by an SV40 vector. 1456 57

Kaposi's sarcoma (KS) develops more frequently in human immunodeficiency virus type 1 (HIV-1)-infected patients. In this study, we report that molecules released by CD8(+)CD28(-) T lymphocytes from HIV-1-infected patients promote endothelial-cell (EC) growth and induce ECs to acquire spindle cell morphology and upregulation of intercellular adhesion molecule-1 (ICAM-1), E-selectin, and vascular endothelial cell growth factor receptor-3 (VEGFR-3) (a typical feature of the KS cell phenotype). The effects observed on ECs cocultured with in vivo activated CD28(-) cells were partly reproduced when ECs were grown in medium containing interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha). At concentrations similar to those found in the supernatant of in vivo activated CD28(-) cells, the two proinflammatory cytokines sustained EC growth and survival only when combined. We, therefore, conclude that CD28(-) T lymphocytes from HIV-1-infected patients exert their effect on ECs through a mechanism involving both IFN-gamma and TNF-alpha. This finding may have wide implications for our basic understanding of the immunopathology of KS.
J Interferon Cytokine Res 2003 Sep
PMID:CD8(+)CD28(-) T lymphocytes from HIV-1-infected patients secrete factors that induce endothelial cell proliferation and acquisition of Kaposi's sarcoma cell features. 1456 61

Leukocyte chemokine receptors (CR) are central to the pathogenesis of many human diseases, including human immunodeficiency virus-1 (HIV-1) infection. Elderly individuals infected with the HIV-1 virus have a shorter disease-free interval and worse clinic outcome. However, the reasons for this are unclear. We recently reported increased CC chemokine receptor (CCR) expression in CD4+ T cells in aged mice, but it is not known if similar changes occur in humans. In addition, it is unclear if the observed differences are related to aged-related expansion in the memory T cell compartment. In this report, we examined the effects of aging on CCR gene expression in human peripheral blood mononuclear cells (PBMCs), CD4+ T cells, and naive/memory T cells. Aging is found to be associated with increased CCR1-5 expression in PBMCs and CD4+ T cells. In addition, although the age-related increases in CCR expression occurred in both naive and memory T cells, the greatest changes were seen in the memory T cell subset. We propose that the observed aging-associated increase in T cell chemokine receptor expression may contribute to the worse clinical outcome of T cell chemokine receptor-dependent disease, such as HIV-1 infection, in the elderly.
J Interferon Cytokine Res 2003 Oct
PMID:Aging is associated with increased human T cell CC chemokine receptor gene expression. 1458 97

Monocyte-derived dendritic cells (DCs) were used as an in vitro model of myeloid DCs in order to determine a minimum marker pattern with which to characterize and distinguish different stages of DC activation and maturation. Phenotypic changes induced on immature DCs by two prototypic stimuli, poly I:C and CD40 ligation, were first examined. Both elicited HLA-DR, CD40, CD86 and CXCR4 upregulation, and CCR5 downregulation, but only CD40 ligand-stimulated DCs became CD83(+)\CCR7(+), whereas poly I:C-stimulated DCs expressed lower CD83 levels and were mostly CCR7(--). CD40 ligation and poly I:C elicited increased production of inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor-alpha, of IL-10 and the CCL5 chemokine, but profiles differed as to higher IL-10, IL-12 and CCL22 (a CCR4 ligand important for T cell recruitment) levels for the former, and of CCL4 and CCL5 for the latter. Thus, a limited set of phenotypic markers, cytokine and chemokine production assays, may be used to distinguish the three stages in the life of DCs: immaturity, activation and full maturation. The ability of purified protein derivative-loaded DCs to stimulate autologous T cells to produce IL-2, IL-4 and interferon-gamma indeed depended on their activation stage and endocytic activity, which decreased upon maturation. We then examined whether ligation of CD4, CCR5 and\or CXCR4, the receptor and coreceptors of human immunodeficiency virus envelope gp120, respectively, affected DC activation or maturation, neither a monoclonal antibody to the gp120-binding site on CD4 nor CCL5 nor CXCL12, the natural ligands of CCR5 and CXCR4, respectively, nor gp120 altered the DC activation and maturation processes.
Eur Cytokine Netw
PMID:Double-stranded RNA stimulation or CD40 ligation of monocyte-derived dendritic cells as models to study their activation and maturation process. 1531 72

Cytokines are small proteins produced by T lymphocytes that mediate immune responses. Those produced by the CD4+ Th1 subset induce cell-mediated immunity, whereas those produced by the CD4+ Th2 subset are more efficient at stimulating immunoglobulin production. The goal of cytokine immunotherapy is prevention or reduction of disease progression through stimulation of cell-mediated immunity (i.e., immune reconstitution) by administration of an exogenous Th1 cytokine such as interleukin-2 (IL-2). Cytokine immunotherapy has its origins in cancer immunobiology where IL-2 has been used successfully to manage several human cancers (metastatic melanoma, acute myelogenous leukemia, and metastatic renal cell carcinoma). More recent work has demonstrated cytokine immunotherapy to be effective at improving immune responses in patients with HIV-1 disease. To explore cytokine immunotherapy for sight-threatening AIDS-related human cytomegalovirus (HCMV) retinitis, we developed a mouse model of experimental murine cytomegalovirus (MCMV) retinitis that employs mice with MAIDS, a retrovirus-induced immunodeficiency syndrome. Systemic cytokine immunotherapy with IL-2, but not with interleukin-12 (IL-12), provides absolute protection against MAIDS-related MCMV retinitis by stimulation of the perforin-mediated pathway of cytotoxicity used by natural killer cells and cytotoxic CD8+ T cells to kill virus-infected cells. Our findings warrant additional studies on the use of cytokine immunotherapy for management of HCMV retinitis (and possibly other opportunistic infections) during HIV-1-induced immunodeficiency. We envision systemic cytokine immunotherapy as an altemative or adjunct to traditional antiviral chemotherapy for optimal management of AIDS-related HCMV retinitis.
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PMID:Interleukin-2 immunotherapy and AIDS-related cytomegalovirus retinitis. 1554 54

Pregnant women are at an increased risk for malarial infection. Plasmodium falciparum accumulates in the placenta and is associated with dysregulated immune function and poor birth outcomes. Malarial pigment (hemozoin) also accumulates in the placenta and may modulate local immune function. In this study, the impact of hemozoin on cytokine production by intervillous blood mononuclear cells from malaria-infected placentas was investigated. There was a dose-dependent, suppressive effect of hemozoin on production of gamma interferon (IFN-gamma), with less of an effect on tumor necrosis factor alpha (TNF-alpha) and interleukin-10, in human immunodeficiency virus-seronegative (HIV(-)) women. In contrast, IFN-gamma and TNF-alpha production tended to increase in HIV-seropositive women with increasing hemozoin levels. Production patterns of cytokines, especially IFN-gamma in HIV(-) women, followed different trends as a function of parasite density and hemozoin level. The findings suggest that the influences of hemozoin accumulation and high-density parasitemia on placental cytokine production are not equivalent and may involve different mechanisms, all of which may operate differently in the context of HIV infection. Cytokine production dysregulated by accumulation of hemozoin or high-density parasitemia may induce pathology and impair protective immunity in HIV-infected and -uninfected women.
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PMID:Hemozoin differentially regulates proinflammatory cytokine production in human immunodeficiency virus-seropositive and -seronegative women with placental malaria. 1555 25


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