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)

Infection of monocyte-macrophages with human immunodeficiency virus may be central to the pathogenesis of the acquired immunodeficiency syndrome. The ability of infected macrophages to prime T cells through IL-1 production was investigated in vitro. Purified human monocytes maintained in suspension culture were infected with strain HIV-DV. Intracellular expression of virus p24 antigen increased from undetectable levels immediately after infection to 13-59% of cells by 10-14 d; infected macrophages remained viable for up to 60 d. Supernatants collected between 14 and 20 d after infection were examined in the murine thymocyte co-mitogenesis assay and demonstrated to contain a potent IL-1 inhibitor, designated contra-IL-1. Contra-IL-1 activity was present in all supernatants examined after 4 d of infection, and peaked coincident with peak p24 antigen expression. Inhibitory activity was not present in uninfected cells. Contra-IL-1 activity eluted after gel filtration with an approximate molecular weight of 9 kD. Inhibitory activity was removed by exposure to heat or acid pH, or by incubation with chymotrypsin or staphylococcal V8 protease. Contra-IL-1 did not inhibit IL-2- or IL-4-dependent proliferation of murine T cell lines. Despite its ability to inhibit IL-1 activity, contra-IL-1 did not interfere with the binding of recombinant IL-1 beta to a fibroblast cell line. Contra-IL-1 inhibited the proliferation of normal peripheral blood mononuclear cells to both concanavalin A and tetanus toxoid; inhibition could be attenuated by the addition of exogenous IL-1. Messenger RNA extracted from infected macrophages was examined by Northern analysis for the presence of message to IL-1 beta. No message was apparent, suggesting that the presence of contra-IL-1 was not obscuring the concomitant release of IL-1. Infected macrophages stimulated with endotoxin generated readily detectable message for IL-1 beta. Spleen macrophages purified from two patients with AIDS complicated by immune thrombocytopenia spontaneously expressed p24 antigen in vitro and released contra-IL-1 activity into the media. Contra-IL-1 may contribute to the immune dysfunction of AIDS.
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PMID:Release of interleukin 1 inhibitory activity (contra-IL-1) by human monocyte-derived macrophages infected with human immunodeficiency virus in vitro and in vivo. 326 91

A model system for cytokine-induced up-regulation of human immunodeficiency virus type 1 (HIV-1) expression in chronically infected promonocyte clones was established. The parent promonocyte cell line U937 was chronically infected with HIV-1 and from this line a clone, U1, was derived. U1 showed minimal constitutive expression of HIV-1, but virus expression was markedly up-regulated by a phytohemagglutinin-induced supernatant containing multiple cytokines and by recombinant granulocyte/macrophage colony-stimulating factor alone. Recombinant interleukin-1 (IL-1), IL-2, interferon-gamma, and tumor necrosis factor-alpha did not up-regulate virus expression. Concomitant with the cytokine-induced up-regulation of HIV-1, expression of membrane-bound IL-1 beta was selectively induced in U1 in the absence of induction of other surface membrane proteins. This cytokine up-regulation of IL-1 beta was not seen in the uninfected parent U937 cell line. These studies have implications for the understanding of the mechanism of progression from a latent or low-level HIV-1 infection to a productive infection with resulting immunosuppression. In addition, this model can be used to delineate the potential mechanisms whereby HIV-1 infection regulates cellular gene expression.
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PMID:Cytokine-induced expression of HIV-1 in a chronically infected promonocyte cell line. 331 29

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

Monocyte-derived macrophages (MDM) were demonstrated to be susceptible to productive infection by the monocytotropic human immunodeficiency virus type 1 (HIV-1) strain HIV-1/Ba-L and by three primary HIV-1 isolates, HIV-1/DAS, HIV-1/PAR and HIV-1/THI. Production of tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and IL-1 beta was monitored between days 3 and 26 after MDM infection. TNF-alpha and IL-6 were detected in cell culture supernatants from days 16 to 21 following HIV-1/DAS, HIV-1/PAR and HIV-1/Ba-L infection, at the time of high viral replication. IL-1 beta was not found at the same time points. TNF-alpha mRNA expression occurred around the peak of both TNF-alpha levels and supernatant RT activities. In HIV-1/THI-infected macrophage cultures no endogenously produced TNF-alpha was observed, despite high levels of HIV-1 in MDM. This result demonstrates that a primary isolate may replicate independently of TNF-alpha in MDM. To investigate the relationship between TNF-alpha and viral replication we used a TNF-alpha synthesis inhibitor, RP 55778. Treatment throughout the course of cell culture resulted in a significant decrease in both TNF-alpha levels and viral production in HIV-1/DAS-, HIV-1/PAR- and HIV-1/Ba-L-infected MDM cultures. This phenomenon is reversed by adding recombinant human TNF-alpha to the RP 55778-treated cell cultures from day 14 post-infection. No effect of RP 55778 was observed in MDM cultures infected with the primary isolate HIV-1/THI, whose replication is independent of TNF-alpha production and therefore remained unchanged after RP 55778 treatment. We conclude that the clinical value of such a drug is directly dependent on the ability of the HIV-1 strains involved to induce TNF-alpha production at the time of viral replication.
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PMID:Infection of human macrophages with an endogenous tumour necrosis factor-alpha (TNF-alpha)-independent human immunodeficiency virus type 1 isolate is unresponsive to the TNF-alpha synthesis inhibitor RP 55778. 751 38

Interleukin-1 beta (IL-1 beta) is a polypeptide produced by a variety of cells of hematological, dermal and neural origin. We have investigated the effect of type I diabetes mellitus and insulin treatment on tissue levels of IL-1 beta using streptozotocin (STZ)-treated mouse as an animal model. Diabetes affected IL-1 beta in a tissue specific manner. For example, IL-1 beta levels (as measured by ELISA) were markedly decreased in the liver and spleen of the STZ diabetic mice. In contrast, the levels of this cytokine remained unalatered in other tissues including kidney, testis, hippocampus and pituitary. Insulin treatment restored the diabetes-related decreases in liver and spleen IL-1 beta levels. Overall, the present data suggest that the abnormalities in hepatic and splenic IL-1 beta levels may contribute, at least in part, to the immunodeficiency and increased susceptibility to infection in diabetes mellitus.
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PMID:Insulin-dependent reduction in hepatic and splenic contents of interleukin-1 beta in experimental diabetes. 759 Jun 11

To investigate the role of B cells in the development of experimental Staphylococcus aureus-induced arthritis, we used X-linked immunodeficiency (xid) mice that carry a Bruton's tyrosine kinase mutation affecting the function of B cells. NFR/N.xid and congenic NFR/N mice were inoculated i.v. with a toxic syndrome toxin-1 producing S. aureus LS-1 strain. B cell-deficient NFR/N.xid mice developed less frequent (p < 0.01) and less severe (p < 0.01) arthritis than NFR/N mice did. These clinical findings were corroborated by histopathologic evaluation, indicating that NFR/N.xid mice had significantly lower (p < 0.01) erosivity of the disease. Interestingly, infected NFR/N.xid mice showed decreased bacterial burden in blood, joints, and other organs compared with the control mice. Serologic studies displayed poor B cell responses to staphylococcal cell walls, toxic shock syndrome toxin-1, and ssDNA, accompanied by a low level of Igs in infected NFR/N.xid mice. More importantly, xid defect affected cytokine profile. The in vitro experiments showed that the lymphocytes from NFR/N.xid mice had low IL-6, but high IFN-gamma production upon stimulation with staphylococcal cell walls compared with NFR/N mice. Furthermore, the in situ hybridization technique revealed the relative increase of IFN-gamma, but marked decrease of IL-1 beta mRNA expression in spleens of infected NFR/N.xid mice. No significant difference in IL-4, IL-10, and TNF-alpha mRNA expression was found between both strains. Our findings demonstrate that B cells may, directly or indirectly, contribute to the pathogenesis of septic arthritis. The results indicate that increased IFN-gamma production along with low IL-6 and IL-1 beta synthesis found in xid mice may provide a more favorable outcome of S. aureus arthritis.
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PMID:Mice with the xid B cell defect are less susceptible to developing Staphylococcus aureus-induced arthritis. 763 57

The aberrant sleep documented in subjects with human immunodeficiency virus (HIV) infection is uniquely important because of the contribution this poor quality sleep makes to the fatigue, disability, and eventual unemployment that befalls these patients. Especially given this importance in clinical care, the research on the prominent sleep changes described in HIV infection remains modest in quantity. The chronic asymptomatic stage of HIV infection is associated with the most intriguing and singular sleep structure changes. Especially robust is the increase in slow wave sleep, particularly in latter portions of the sleep period. This finding is rare in other primary or secondary sleep disorders. The sleep structure alterations are among the most replicable of several pathophysiological sequelae in the brain associated with early HIV infection. It is unlikely that these sleep architecture changes are psychosocial in etiology, and they occur before medical pathology is evident. They are not associated with stress, anxiety, or depression. Evidence is accumulating to support a role for the somnogenic immune peptides tumor necrosis factor (TNF)alpha and interleukin (IL-1 beta) in the sleep changes and fatigue commonly seen in HIV infection. These peptides are elevated in the blood of HIV-infected individuals, and are somnogenic in clinical use and animal models. The peripheral production of these peptides may also have a role in the regulation of normal sleep physiology. The lentivirus family contains both HIV and the feline immunodeficiency virus (FIV). The use of the FIV model of HIV infection may provide a way to further investigate the mechanism of a neurotropic, neurotoxic virus initiating the immune acute phase response and affecting sleep. Neurotropic lentivirus infection is a microbiological probe facilitating neuroimmune investigation.
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PMID:Lentiviral infection, immune response peptides and sleep. 779 94

We have previously shown that lymphocytic cells bind to cultured syncytiotrophoblast and that this may be important in the lymphocyte-mediated infection of trophoblast with the human immunodeficiency virus (HIV). Leukocyte-trophoblast adhesion may also have implications for normal trophoblast function. The following experiments were designed to characterize the adhesion systems that mediate the attachment of lymphocytic cells to trophoblast. Adhesion was assayed by labelling lymphocytic MOLT-4, clone 8 cells with the fluorescent marker, calcein-AM, and then incubating them with primary cultures of human syncytiotrophoblast. Adhesion was stimulated by pretreatment of the trophoblast cultures with several cytokines either alone or together. These included tumor necrosis factor-alpha (TNF-alpha), granulocyte/macrophage-colony stimulating factor (GM-CSF), interleukin-1 beta (IL-1 beta) and interferon-gamma (IFN-gamma). Stimulation was time- and dose-dependent. In contrast, preincubation of trophoblast cultures with anti-TNF-alpha antibodies for 2 days reduced MOLT adhesion by almost 50%. Preincubation with other anti-cytokine antibodies had no significant effect on adhesion. In other experiments, adhesion was measured in the presence of antibodies to known adhesion molecules. Adhesion was reduced by 50% in the presence of antibodies to alpha 4 integrin or beta 1 integrin. When present together, these antibodies reduced adhesion by almost 85%. Incubation in the presence of antibodies to the very late activation antigen-4 (VLA-4; alpha 4 beta 1 integrin) counter-receptors, VCAM-1 and CS-1, was without effect. Adhesion was also unaffected by antibodies to LFA-1, ICAM-1, ICAM-2, LFA-2, or LFA-3. These results suggest that adhesion is mediated by an adhesion system consisting of lymphocyte VLA-4 (alpha 4 beta 1) and an as yet unidentified counter receptor on trophoblast.
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PMID:Effect of cytokines and anti-adhesion molecule antibodies on the adhesion of lymphocytic cells to human syncytiotrophoblast. 780 71

Patients with end-stage renal disease present an immunodeficiency that paradoxically coexists with activation of most immunocompetent cells, and the roles of chronic uremia and maintenance dialysis are poorly understood. We determined circulating levels of IL-1 beta and IL-1Ra, TNF-alpha and its soluble receptors (TNF-sR55 and TNF-sR75), and activation markers of T cells (soluble CD25), B cells (soluble CD23), and monocytes (neopterin) in a large cohort of undialyzed patients at various stages of chronic renal failure and in dialyzed patients on maintenance hemodialysis or chronic peritoneal dialysis. The progression of uremia was associated with a gradual increase in soluble CD25, CD23, and especially neopterin levels. Although IL-1 beta could not be detected, IL-1Ra levels were significantly increased from the earliest stage of renal failure. Plasma levels of TNF-alpha, TNF-sR55, and TNF-sR75 progressed with the severity of renal failure and correlated with soluble CD25, CD23, and neopterin levels, whereas IL-1Ra levels correlated exclusively with TNF-sR55 levels. Compared with undialyzed patients, levels of IL-1 beta were higher in patients on maintenance hemodialysis, whereas those of IL-1Ra were lower and decreased further at the end of dialysis sessions. In contrast, both TNF-sR55 and TNF-sR75 levels were significantly higher than in undialyzed patients and increased further at the end of dialysis sessions in the absence of an increase of TNF-alpha. Such an imbalance between cytokines and their inhibitors may play a pivotal role in the multifaceted process of immune dysfunction.
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PMID:Balance between IL-1 beta, TNF-alpha, and their specific inhibitors in chronic renal failure and maintenance dialysis. Relationships with activation markers of T cells, B cells, and monocytes. 781 91


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