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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A promonocytic cell model was used to investigate cytokine gene transcription in U937 and U9-IIIB cells chronically infected with human immunodeficiency virus type 1 (HIV-1). The production of interferon (alpha-1 interferon [IFN-alpha 1], IFN-alpha 2, and IFN-beta), interleukin (interleukin 1 alpha [IL-1 alpha], IL-1 beta, and IL-6), and tumor necrosis factor alpha (TNF-alpha) mRNA was characterized by quantitative polymerase chain reaction mRNA phenotyping in U937 and U9-IIIB cells following coinfection with Sendai paramyxovirus or stimulation with lipopolysaccharide (LPS). Chronic HIV-1 infection of U9-IIIB cells resulted in a low constitutive level of transcription of TNF and IL-1 genes but not IFN genes; however, when the cells were coinfected with Sendai virus, 10- to 20-fold higher levels of IFN-beta, IL-1 beta, IL-6, and TNF-alpha mRNA were observed in U9-IIIB cells than in similarly induced U937 cells. The enhanced levels of cytokine RNA in virus-infected U9-IIIB cells were also accompanied by higher levels of IFN antiviral activity and TNF secretion than in U937 cells. Transcript levels for IFN-alpha 1 and IFN-alpha 2 were equivalently induced in virus-infected U937 and U9-IIIB cells, indicating that a generalized derepression of cytokine gene expression did not occur as a consequence of HIV-1 infection. When LPS was used as an inducer, a distinct pattern of cytokine gene expression was detected in U9-IIIB cells. TNF-alpha and IL-1 beta but not IFN-alpha or IFN-beta transcripts were induced by LPS. These results suggest that HIV-1 infection of promonocytic cells may prime or sensitize cells such that subsequent antigenic challenge leads to coordinate enhancement of cytokine gene expression.
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PMID:Coordinate enhancement of cytokine gene expression in human immunodeficiency virus type 1-infected promonocytic cells. 224 88

Interferon alpha (IFN-alpha) induces significant antiretroviral activities that affect the ability of human immunodeficiency virus (HIV) to infect and replicate in its principal target cells, CD4+ T cells and macrophages. A major endogenous source of IFN-alpha during any infection is the macrophage. Thus, macrophages have the potential to produce both IFN-alpha and HIV. In this study, we examined the production of IFN-alpha and other cytokines by macrophage colony-stimulating factor (M-CSF)-treated cultured monocytes during HIV infection. Tumor necrosis factor alpha (TNF-alpha), interleukin 1 beta (IL-1 beta), IL-6, IFN-omega, or IFN-beta were not detected nor was the mRNA expressed in either uninfected or HIV-infected monocytes. However, both uninfected and HIV-infected monocytes produced high levels of each of these cytokines after treatment with synthetic double-stranded RNA [poly(I).poly(C)]. Uninfected monocytes also produced high levels of IFN-alpha after treatment with poly(I).poly(C), Newcastle disease virus, or herpes simplex virus. In marked contrast to the preceding observations, HIV-infected monocytes produced little or no IFN-alpha before or after treatment with any of these agents. The absence of detectable IFN-alpha activity and mRNA in poly(I).poly(C)-treated HIV-infected monocytes was coincident with high levels of 2',5' oligoadenylate synthetase and complete ablation of HIV gene expression. The antiviral activity induced by poly(I).poly(C) may be a direct effect of this synthetic double-stranded RNA or secondary to the low levels of IFN-beta and IFN-omega produced by infected cells. The markedly diminished capacity of HIV-infected monocytes to produce IFN-alpha may reflect a specific adaptive mechanism of virus to alter basic microbicidal functions of this cell. The inevitable result of this HIV-induced cytokine dysregulation is virus replication and persistence in mononuclear phagocytes.
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PMID:A selective defect of interferon alpha production in human immunodeficiency virus-infected monocytes. 198 24

The production of interleukin-1 beta (IL-1 beta), IL-6, and tumor necrosis factor alpha (TNF-alpha) by fresh peripheral blood mononuclear cells was evaluated after exposure to human immunodeficiency virus (HIV) or purified recombinant HIV-1 envelope glycoprotein (rgp120). To exclude the role of contaminating endotoxin in this study, all media were subjected to ultrafiltration and reagents contained less than 25 pg of endotoxin per ml by Limulus assay. Under endotoxin-free conditions, no increases in IL-1 beta, IL-6, or TNF-alpha mRNA or protein were detectable in cell cultures exposed to HIV-1, HIV-2, or rgp120 (0.1 to 10 micrograms/ml), as compared with cytokine levels in mock-exposed cultures. However, concentrations of endotoxin (lipopolysaccharide) as low as 0.5 ng/ml induced significant production of mRNA and protein for these three cytokines. Preincubation of mononuclear cells with "shake" HIV-1 preparations and also mock-infected shake preparations prior to lipopolysaccharide stimulation resulted in a two- to threefold increase in IL-1 beta and TNF-alpha production. This priming effect was not observed with rgp120 (0.1 to 10 micrograms/ml) or standard HIV-1 or mock-infected supernatants, suggesting the presence of biologically active material independent of virus in the shake preparations. Our studies indicate that, in the absence of endotoxin, HIV-1, HIV-2, and HIV gp120 do not induce production of IL-1 beta, IL-6, or TNF-alpha by peripheral blood mononuclear cells.
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PMID:Human immunodeficiency virus does not induce interleukin-1, interleukin-6, or tumor necrosis factor in mononuclear cells. 233 21

Figure 1 depicts some of the potential interactions of the interleukins. Among the substances discussed here, only IL-2 has been used to any large degree in a clinical series. Other cytokines not discussed including some of the colony stimulating factors, tumor necrosis factor and the interferons have also been used in clinical trials. Undoubtedly as we learn more about interleukins IL-1 through IL-7, clinical applications will become apparent. For the allergist/immunologist there are two areas of greatest potential interest. The first of these is in treating immunodeficiency states. Preliminary studies of the use of IL-2 in patients with T cell dysfunction suggest that this substance may be useful in treating selective T cell disorders. IL-4, 5, and 6 all have some influence on B cell function. It is likely that in the near future one or more of these agents will be used clinically. It is also clear that the interleukins have the potential to influence basic mechanisms known to be important in allergic disease. IL-3 is the major factor influencing mast cell growth. IL-4 among other things, promotes B cells to switch to IgE synthesis as well as to induce Fc epsilon RII receptors on B cells. IL-5 is important in the differentiation and growth of eosinophils. Finally, IL-6 is the terminal differentiation factor that causes B cells to become plasma cells. The next few years should result in an even better understanding of the role of each of these interleukins. It is likely that such information will greatly expand the horizons for understanding the pathogenesis of many immunologically mediated diseases and will provide the basis for new modalities of treatment.
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PMID:Interleukins in immunologic and allergic diseases. 267 43

The expression of Fc epsilon R on human lymphocytes was studied with the anti-Fc epsilon R mAbs. Fc epsilon R was expressed on most mu+,delta+ circulating B cells, whereas T cells did not express Fc epsilon R even in patients with hyper-IgE syndrome. B cells with gamma, alpha, or epsilon phenotype did not express Fc epsilon R, moreover its expression could not be induced, suggesting that the Fc epsilon R expression was correlated with isotype switching. mu+delta+ B cells in bone marrow did not express Fc epsilon R, but PHA-sup (supernatant from PHA-stimulated cell cultures) could induce its expression, and the addition of IgE augmented this induction. Recombinant IL-2, IL-1, IFN-gamma or -beta, or purified B cell differentiation factor (BSF-2 B cell-stimulatory factor 2) could not induce Fc epsilon R expression in bone marrow B cells. IFN-gamma inhibited the Fc epsilon R expression induced by PHA-sup, suggesting that the human counterpart of BSF-1 may be responsible for Fc epsilon R expression in bone marrow B cells. B cells from patients with common variable immunodeficiency and ataxia telangiectasia did not express Fc epsilon R, but PHA-sup could induce its expression, indicating that circulating B cells of these patients are at a differentiation stage similar to B cells in bone marrow. The study showed that Fc epsilon R is a B cell-specific differentiation marker, the expression of which is restricted to a defined stage of B cell differentiation.
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PMID:Fc epsilon receptor, a specific differentiation marker transiently expressed on mature B cells before isotype switching. 294 90

As an attempt to elucidate the pathogenesis of human immunodeficiency virus type 1 (HIV-1)-related cytopenia, the effects of infection of long-term primary bone marrow culture (LTBMC)-derived adherent cells on hematopoiesis were investigated. Productive infection could then be established only when using monocytotropic strains HIV-1Ba-L, HIV-1Ada, and HIV-1JR-FL but not with lymphocytotropic strain HIV-1LAI. Culture supernatants were tested for major cytokines involved in the regulation of hematopoiesis: neither IL-3 nor GM-CSF were detectable in the infected or noninfected cultures; in contrast, TGF-beta, TNF-alpha, MIP-1 alpha, Steel Factor, and IL-6 were detected at all times in established LTBMCs, but their levels were not consistently altered by virus replication. In vitro functional analysis by colony and long-term culture assays showed that HIV-1 infection failed to alter either the kinetics or the number of hematopoietic progenitors produced by the stromal layers; it did not interfere with the clonogenicity of exogeneous CD34+ cells in semisolid assays, and no difference was observed relative to the controls when HIV-1-infected stromal layers were tested for their ability to sustain long-term hematopoiesis. These results show that productive and sustained virus replication in the macrophage component of LTBMCs does not significantly alter the profile of major cytokines involved in regulating hematopoiesis, nor is it sufficient by itself for altering in vitro hematopoiesis under the baseline conditions used.
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PMID:In vitro infection of bone marrow-adherent cells by human immunodeficiency virus type 1 (HIV-1) does not alter their ability to support hematopoiesis. 748 69

HIV-infected patients exhibit defects in B cell differentiation and in the IL-6 response of B cells, in association with autoantibody formation against T cells. These autoantibodies have been implicated as important factors in the development of immunodeficiency disease. As the restoration of defective B cell responses might prevent autoantibody formation and the resulting immunosuppression, we studied whether in vitro treatment with recombinant IL-2 (rIL-2), recombinant IL-4 (rIL-4) or recombinant IL-6 (rIL-6) might restore the response of B cells of HIV-infected patients. B cells of 6 HIV-negative hemophilia patients, 4 HIV-positive patients at CDC stage II, III, 4 HIV-positive patients at CDC stage IV, and 6 healthy controls were tested in Staphylococcus aureus Cowan I (SAC-I)-stimulated B cell cultures and Pokeweed mitogen (PWM)-stimulated allogeneic B and T cell cocultures. B cell differentiation was assessed in a reverse hemolytic plaque assay and by ELISA determination of IgM, IgG and IL-6 in culture supernatants. In vitro application of rIL-6 resulted in suppression of both elevated unstimulated and mitogen-stimulated B cell responses in a dose-dependent manner which was in part due to feedback inhibition. PWM- and SAC-I-stimulated IgG and IgM responses, respectively, could be restored after addition of 10 U/ml rIL-2 in HIV-negative patients, but not in HIV-positive patients. Addition of rIL-4 to cultures resulted in suppression of both unstimulated and mitogen-stimulated IL-6 secretion and B cell responses. Severely depressed B cell responses in CDC IV patients were not significantly affected by cytokine application. These results indicate that defective Ig responses in HIV-negative patients may be restored by rIL-2 treatment whereas HIV-induced B cell defects are not corrected by supply of T cell help or cytokines promoting B cell growth and differentiation.
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PMID:In vitro cytokine treatment of B cell defects in HIV-infected hemophilia patients. 748 89

Elevation of serum interleukin-1 beta (IL-1 beta) levels, and to a lesser degree tumor necrosis factor alpha levels, was found in cachectic human immunodeficiency virus (HIV)-infected African patients without concurrent opportunistic infection or neoplasia (HIV wasting syndrome). A heterogeneous pattern of elevations of cytokine levels, including mild elevations of IL-1 beta and pronounced elevations of IL-6 levels, was found in other cachectic states.
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PMID:Differential elevation of circulating interleukin-1 beta, tumor necrosis factor alpha, and interleukin-6 in AIDS-associated cachectic states. 749 13

In the present study we have observed that interleukin (IL) 1 alpha or IL-1 beta directly induced expression of human immunodeficiency virus (HIV) in the latently infected human promonocytic cell line U1. In addition, IL-1 synergized with IL-6, but not with tumor necrosis factor, in the upregulation of virus expression in U1 cells as measured by accumulation of steady-state mRNAs and production of reverse transcriptase activity. The HIV inductive effect of IL-1 was blocked by transforming growth factor beta, anti-IL-1 antibodies, or monoclonal antibodies directed to the type 1, but not to the type 2, cell surface receptor for IL-1; the latter actually caused enhancement of the IL-1-mediated effect. Unlike tumor necrosis factor alpha, IL-1 either alone or in combination with IL-6 did not induce activation of the transcription activating factor NF-kappa B above the constitutive levels of unstimulated U1 cells. Finally, the IL-1 receptor antagonist effectively blocked IL-1-mediated direct and synergistic inductive effects on virus production. Thus, IL-1 may be an important mediator of HIV expression, and blocking of IL-1 expression and/or its effects may have a potential therapeutic role in the inhibition of HIV expression in infected individuals.
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PMID:Interleukin 1 induces expression of the human immunodeficiency virus alone and in synergy with interleukin 6 in chronically infected U1 cells: inhibition of inductive effects by the interleukin 1 receptor antagonist. 750 10

Induction of an IgE response involves several discrete steps: 1) induction of epsilon germ line transcription, 2) DNA recombination, and 3) mature RNA transcription/translation. Here we show that ligation of B cell CD58 by CD2, its natural ligand on T cells, or by mAb, provides a novel IL-4-dependent signal for the latter two steps. Highly purified human B cells were induced to produce IgE by costimulation with IL-4 and CD58 mAb. Although CD58 ligation alone was unable to induce epsilon germ-line transcription, in concert with IL-4-stimulated epsilon germ-line transcription it induced the appearance of productive epsilon transcripts and IgE production. The direct involvement of CD2 was demonstrated: B cells cultured with IL-4 plus murine T hybridoma cells transfected with human CD2 produced IgE. A CD40 Fc fusion protein had no effect on CD58-driven IgE production while inhibiting CD40-dependent responses. Furthermore, cells from patients with common variable immunodeficiency produced IgE in response to IL-4 plus CD40 mAb but not to IL-4 plus CD58 mAb. CD58-driven IgE synthesis was IFN-gamma independent and was not enhanced by exogenous IL-6. Functional differences between CD40 and CD58 IgE stimulation were demonstrated. Thus, the CD2:CD58 ligand/counterligand system provides an alternative pathway by which cell contact signaling may regulate IgE. Given the relative importance of CD2 triggering on mucosal T cells and the mucosal location of IgE production, this may be especially true on mucosal surfaces.
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PMID:CD58 (LFA-3) stimulation provides a signal for human isotype switching and IgE production distinct from CD40. 751 20


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