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)

The demonstration that macrophages express CXCR4 has led to a reexamination of their susceptibility to human immunodeficiency (HIV)-1 X4 strains. Here, we examined the susceptibility to X4 HIV-1Lai of two previously characterized macrophage populations, obtained either as 1) adherent cells of five-day cultures of blood mononuclear cells (PBMC), followed by two days without nonadherent PBMC nor added cytokines (MDM-5d); or 2) as adherent cells recovered from one-hour incubation of PBMC, which were cultured for seven days with macrophage colony-stimulating factor (MDM-MCSF). Exposing MDM-5d or MDM-MCSF to HIV-1Lai did not lead to productive infection, as indicated by a lack of (MDM-MCSF) or low (MDM-5d) viral p24 levels in culture supernatants. However, MDM-5d vigorously transmitted HIV-1 Lai to autologous T lymphocytes, which was not the case of HIV-1Lai-exposed MDM-MCSF. PCR analysis of the LTR RU5 region showed that X4 HIV-1Lai entered into both types of macrophages in the same manner as R5 HIV-1 BaL. However, in contrast to MDM-5d, there was a block of HIV-1 Lai retrotransciption in MDM-MCSF. Cytokine profile analysis of the two types of macrophages showed that TNF-alpha, IL-6 and RANTES levels were higher in MDM-5d than in MDM-MSCF, while the IL10 level was higher in MDM-MCSF, both producing similar IL16 levels. Altogether, these data indicate that HIV-1 X4 strains enter into macrophages but that their replication is blocked thereafter in a different manner according to the activation status of the cells.
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PMID:The susceptibility of macrophages to human immunodeficiency virus type 1 X4 isolates depends on their activation state. 1123 83

The influence of host cytokine response on viral load, disease progression, and neurologic lesions was investigated in the simian immunodeficiency virus (SIV)-infected macaque model of AIDS. Cytokine gene expression (interleukin-1beta [IL-1beta], IL-2, IL-6, IL-10, gamma interferon [IFN-gamma], and tumor necrosis factor alpha [TNF-alpha]) and viral loads were evaluated by semiquantitative reverse transcription-PCR in lymph nodes of 5 control animals and 28 animals infected with SIVmac251 at the terminal stages of AIDS. Infected animals showed higher expression of IFN-gamma, IL-6, and IL-10 mRNAs compared with controls. Levels of all cytokines were comparable between animals with rapid (survival, <200 days) or slow/normal (survival, >200 days) disease progression. However, among rapid progressors, the eight animals with SIV encephalitis had a unique cytokine profile (increased IL-2, IL-6, and IFN-gamma) that was associated with higher viral loads. These observations provide evidence that host cytokine responses may influence SIV neuropathogenesis independent of disease progression.
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PMID:Macaques with rapid disease progression and simian immunodeficiency virus encephalitis have a unique cytokine profile in peripheral lymphoid tissues. 1128 99

Since interleukin (IL-)2, IL-10 and IL-12 may contribute to the pathogenesis of human immune deficiency virus (HIV) infection we examined the effect of interferon (IFN)-alpha on these cytokines in cultures of various subsets of peripheral blood mononuclear cells (PBMC) in ten HIV-infected patients and ten healthy controls. Our main findings were: (1) IFN-alpha markedly enhanced IL-10 levels in a dose-dependent manner in both lipopolysaccharide (LPS)- and phytohaemagglutinin (PHA)-stimulated PBMC, as well as in anti-CD3- and anti-CD3/anti-CD28-stimulated T cells in both HIV-infected patients and controls. (2) In contrast, IFN-alpha had a downregulatory effect on IL-10 levels in Candida -stimulated PBMC,with particularly strong suppressive effect in HIV-infected patients. (3) Furthermore, IFN-alpha had a significant but modest stimulatory effect on IL-2 levels in PHA- and Candida -stimulated PBMC and anti-CD3-stimulated T cells. (4) IFN-alpha enhanced IL-12 levels in a dose-dependent manner in LPS-stimulated PBMC in both patients and controls. Our findings that IFN-alpha markedly enhanced IL-10 and modestly enhanced IL-2 and IL-12, suggest a net immunosuppressive effect of IFN-alpha in HIV-infected patients, possibly contributing to progression of immunodeficiency in these patients.
Cytokine 2001 Apr 07
PMID:Complex effects of interferon-alpha on the cytokine network in HIV infection--possible contribution to immunosuppression. 1129 93

The chemokines and their receptors have been receiving exceptional attention in recent years following the discoveries that some chemokines could specifically block human immunodeficiency virus type 1 (HIV-1) infection and that certain chemokine receptors were the long-sought coreceptors which, along with CD4, are required for the productive entry of HIV-1 and HIV-2 isolates. Several chemokine receptors or orphan chemokine receptor-like molecules can support the entry of various viral strains, but the clinical significance of the CXCR4 and CCR5 coreceptors appear to overshadow a critical role for any of the other coreceptors and all HIV-1 and HIV-2 strains best employ one or both of these coreceptors. Binding of the HIV-1 envelope glycoprotein gp120 subunit to CD4 and/or an appropriate chemokine receptor triggers conformational changes in the envelope glycoprotein oligomer that allow it to facilitate the fusion of the viral and host cell membranes. During these interactions, gp120 appears to be capable of inducing a variety of signaling events, all of which are still not defined in detail. In addition, the more recently observed dichotomous effects, of both inhibition and enhancement, that chemokines and their receptor signaling events elicit on the HIV-1 entry and replication processes has once again highlighted the intricate and complex balance of factors that govern the pathogenic process. Here, we will review and discuss these new observations summarizing the potential significance these processes may have in HIV-1 infection. Understanding the complexities and significance of the signaling processes that the chemokines and viral products induce may substantially enhance our understanding of HIV-1 pathogenesis, and perhaps facilitate the discovery of new ways for the prevention and treatment of HIV-1 disease.
Cytokine Growth Factor Rev
PMID:Human immunodeficiency virus type-1 and chemokines: beyond competition for common cellular receptors. 1132 4

Interleukin-18 (IL-18), previously known as interferon-gamma (IFN-gamma)-inducing factor (IGIF), is a proinflammatory cytokine expressed by activated macrophages that acts in synergy with IL-12 as an important amplifying factor for IFN-gamma production and Th1 development. To study the effect of IL-18 on a lentiviral infection, we cloned the IL-18 gene from a rhesus macaque and constructed replication-competent simian immunodeficiency virus (SIV) that expressed either the precursor pro-IL-18 (SIV(IL-18)) or the mature form (SIV(mIL-18)) of IL-18. The predicted amino acid sequence for rhesus IL-18 had 96% homology with the human one, differing in only 8 of 193 residues. SIV(IL-18) and SIV(mIL-18) replicated more slowly than control viruses in the CEM x 174 cell line and resulted in the development of chronically infected cell lines that expressed high levels of infectious SIV. The cell line generated by SIV(IL-18) released large quantities of IL-18 into the supernatant, whereas the one obtained from SIV(mIL-18) showed the accumulation of IL-18 in the cytoplasm. Similarly, SIV(IL-18) and SIV(mIL-18) replicated more slowly than the unmodified viral vector in rhesus peripheral blood mononuclear cells (PMBC), but only SIV(IL-18) expressed biologically active IL-18. These experiments show that the precursor form of IL-18 is necessary for the efficient release of the cytokine and that IL-18 does not promote increased replication of SIV in rhesus PBMC.
J Interferon Cytokine Res 2001 Mar
PMID:Expression of the interleukin-18 gene from rhesus macaque by the simian immunodeficiency virus does not result in increased viral replication. 1133 Oct 40

We studied cytokine production by stimulated peripheral blood mononuclear cells from 55 HIV-infected children born to HIV-infected mothers, and compared it to that of exposed, but uninfected, age-matched children. Cytokine production was quantified using a commercially available specific ELISA kit. Cell proliferation was evaluated by incorporation of ((3)H) thymidine. A significant defect in type 1 cytokine production of IFN-gamma and IL-2 in HIV-infected children compared to controls was observed, but without a concomitant increase in type 2 cytokines. Indeed, IL-5 production was even lower in HIV-infected children than in controls, the IL-5 decrease being the best predictive marker of immunodeficiency. Furthermore, IL-5 levels were decreased from the early phases of HIV infection, being significantly lower in the clinical category B with respect to controls, and in AIDS with respect to both controls and children in category A. Such a strong correlation with the stage of infection has not been previously described in HIV-infected children. In addition, we found a correlation between SI/X4 viral phenotype and lower IL-5 levels. Our data suggest a dysfunctional cytokine production by PBMC from HIV-infected children as regards both Th1 and Th2 cytokines resulting from quantitative as well as qualitative defects induced by HIV-1.
Eur Cytokine Netw
PMID:Impaired interleukin-5 (IL-5) production by T cells as a prognostic marker of disease progression in human immunodeficiency virus type 1 (HIV-1)-infected children. 1139 13

Soluble factors released by intra-cerebral activated cells are implicated in neuronal alterations during central nervous system inflammatory diseases. In this study, the role of the CD23 pathway in astrocyte activation and its participation in human immunodeficiency virus-1 (HIV-1)-induced neuropathology were evaluated. In human primary astrocytes, CD23 protein membrane expression was dose-dependently upregulated by gp120. It was also upregulated by gamma-interferon (gamma-IFN) and modulated by interleukin-1-beta (IL-1beta) whereas microglial cells in these stimulation conditions did not express CD23. Cell surface stimulation of CD23 expressed by astrocytes induced production of nitric oxide (NO) and IL-1beta which was inhibited by a specific inducible NO-synthase (iNOS) inhibitor (aminoguanidine), indicating the implication of this receptor in the astrocyte inflammatory reaction. On brain tissues from five out of five patients with HIV-1-related encephalitis, CD23 was expressed by astrocytes and by some microglial cells, whereas it was not detectable on brain tissue from five of five HIV-1-infected patients without central nervous system (CNS) disease or from two of two control subjects. In addition, CD23 antigen was co-localized with iNOS and nitrotyrosine on brain tissue from patients with HIV1-related encephalitis, suggesting that CD23 participates in iNOS activation of astrocytes in vivo. In conclusion, CD23 ligation is an alternative pathway in the induction of inflammatory product synthesis by astrocytes and participates in CNS inflammation.
Cytokine 2001 Jul 21
PMID:Role of CD23 in astrocytes inflammatory reaction during HIV-1 related encephalitis. 1150 85

Extrapulmonary tuberculosis is presumably a marker of underlying immunodeficiency, but cytokine response pathways in these patients have not been well studied. Cytokine responses of peripheral blood mononuclear cells from human immunodeficiency virus-seronegative adults with prior culture-confirmed extrapulmonary tuberculosis were compared with those of persons with latent Mycobacterium tuberculosis infection. Mitogen-stimulated interferon (IFN)-gamma production, interleukin (IL)-12 production, and IFN-gamma receptor- and IL-12 receptor-mediated cytokine production did not differ between case patients and control patients. However, median resting IL-8 production was significantly lower in case patients than control patients (8051 vs. 19,290 pg/mL; P=.009). In addition, the median tumor necrosis factor (TNF)-alpha response was lower in case patients than control patients after stimulation with lipopolysaccharide (833 vs. 1149 pg/mL; P=.06) and lipopolysaccharide plus IFN-gamma (3301 vs. 4411 pg/mL; P=.04). These abnormalities in resting IL-8 and lipopolysaccharide-induced TNF-alpha production were not associated with IFN-gamma or IL-12 abnormalities and were detected up to several years after cure of disease, suggesting an abnormality in innate immunity.
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PMID:Human immunodeficiency virus-seronegative adults with extrapulmonary tuberculosis have abnormal innate immune responses. 1152 68

It has been postulated that the inflammatory response that occurs after cutaneous wounding is a prerequisite for healing and that inflammatory cytokines, such as interleukin-6 (IL-6) are involved in this process. We showed previously that IL-6-deficient mice display delayed wound healing, which could be reversed by administration of a murine IL-6 expression plasmid or recombinant murine IL-6 (rMuIL-6). In the present study, we observed that delayed cutaneous wound healing, which occurs as a result of glucocorticoid-induced immunosuppression, can also be reversed by rMuIL-6, as evidenced by epithelialization, granulation tissue formation, and wound closure. In vehicle control mice, rMuIL-6 did not augment healing but rather delayed the process. Immunochemical studies indicated that the expression of matrix metalloproteinase-10 (MMP-10) was increased in dexamethasone-treated mice and that rMuIL-6 treatment reduced its expression, indicating that IL-6 may influence dermal matrix formation and, specifically, collagen synthesis. These results demonstrate that IL-6 can restore abnormal wound repair that occurs in immunodeficiency and suggest its use as a potential therapy.
J Interferon Cytokine Res 2001 Aug
PMID:Interleukin-6 treatment augments cutaneous wound healing in immunosuppressed mice. 1155 38

As the therapeutic use of interferon-alpha (IFN-alpha) is limited by a dose-dependent toxicity and variable efficacy, ways of improving the therapeutic index of the cytokine are being sought. Murabutide (N-acetyl muramyl-L-alanyl-D-glutamine-O-n-butyl-ester) (ISTAC Biotechnology, Lille, France) is a safe synthetic and clinically acceptable immunomodulator that enhances the biologic activities of IFN-alpha in different experimental models. We evaluated in healthy human volunteers tolerance of the coadministration of Murabutide with increasing doses of IFN-alpha. The simultaneous administration of the two drugs was well tolerated without any increased or prohibiting toxicity, and all recipients experienced side effects that were similar to those observed after the administration of IFN-alpha alone. We also profiled the serum levels of cytokines induced following coinjection of the two drugs. We mostly detected an induction of anti-inflammatory cytokines and of human immunodeficiency virus type 1 (HIV-1)-suppressive beta-chemokines, in the absence of release of key proinflammatory cytokines. Therefore, the simultaneous administration of Murabutide and IFN-alpha is well tolerated and does not lead to increased toxicity. In addition, the selectivity in the profile of cytokines and chemokines induced following the coadministration of Murabutide and IFN-alpha points to the potential use of this combination in the treatment of inflammatory diseases and chronic viral infections.
J Interferon Cytokine Res 2001 Sep
PMID:Clinical tolerance and profile of cytokine induction in healthy volunteers following the simultaneous administration of ifn-alpha and the synthetic immunomodulator murabutide. 1157 59


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