UMLS:C0021311 - FACTA Search

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Query: UMLS:C0021311 (Infection)
38,178 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

IL-10 has been shown to be capable of down-regulating several aspects of macrophage function. This study was undertaken to define the association between IL-10 and HIV-1 infection in human macrophages. Infection of macrophages with a monocytotropic strain of the human immunodeficiency virus, HIV-BaL, resulted in expression of IL-10 mRNA within 3 to 12 h after infection, as determined by the reverse transcriptase PCR. Biologically active IL-10 was detected in supernatants from HIV-1-infected macrophages as early as 12 h post-infection. The addition of human rIL-10 to HIV-1-infected macrophage cultures resulted in a significant decrease in the viral replication. In addition, exogenous IL-10 blocked the ability of TNF-alpha to elevate viral replication. To determine whether IL-10 was associated with in vivo infection, lymph nodes from AIDS patients were examined for the presence of IL-10 mRNA by using PCR. IL-10 mRNA was evident in all lymph node tissue examined, but was absent in normal lymph node biopsies. These in vitro and in vivo findings demonstrate a strong and heterogeneous association between HIV-1 infection and IL-10.
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PMID:IL-10 is induced during HIV-1 infection and is capable of decreasing viral replication in human macrophages. 752 49

Infection of immune cells with HIV induces dysregulation of cytokines which may play a vital role in HIV pathogenesis. We analysed the expression of T helper type 1 (Th1) (interferon-gamma (IFN-gamma)) and Th2 (IL-4, IL-10) type cytokines in peripheral blood lymphocytes (PBL) from HIV+ patients. The semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) analysis revealed that IFN-gamma mRNA in unstimulated PBL was significantly decreased and IL-10 mRNA was significantly upregulated in patients with < 400 CD4+ T cells/mm3 (n = 30) as compared to patients with > 400 CD4+ T cells/mm3 (n = 6) and normal controls (n = 16). In addition, IL-10 mRNA levels were inversely associated with IFN-gamma expression. Similar results were obtained by measuring IL-10 production in the supernatants of PBL cultured in vitro without stimulation by employing an enzyme immunosorbent assay (ELISA). However, the levels of IL-4 and IFN-gamma produced by unstimulated PBL were undetectable by ELISA. Mitogen stimulation of PBL revealed two groups of HIV+ individuals based on IL-10 production. PBL from one set of individuals produced low levels of IL-10 (low IL-10 producers) whereas the other group produced IL-10 comparable to that of normal controls (IL-10 producers). Production of IL-4 was significantly reduced in HIV+ individuals with < 400 CD4+ T cells/mm3 as compared to the normal controls. However, ability to produce IFN-gamma by mitogen-stimulated total PBL and CD4+ purified cells was not impaired in HIV+ individuals. These results suggest that unstimulated and mitogen-stimulated PBL of HIV+ individuals exhibit dysregulation of Th2 type cytokines which may play a role in HIV immunopathogenesis.
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PMID:Expression of IL-10, IL-4 and interferon-gamma in unstimulated and mitogen-stimulated peripheral blood lymphocytes from HIV-seropositive patients. 755 96

The effect of recombinant murine IL-12 (rIL-12) or anti-IL-12 antibody administration on resistance to murine listeriosis was investigated. Mice given a single 0.5 micrograms dose of rIL-12 had 1.5 log10 fewer listeriae in their spleens and livers as compared with control infected mice 3 days after L. monocytogenes challenge. Conversely, administration of anti-IL-12 IgG caused an equivalent increase in the cfu of L. monocytogenes recovered from the spleens and livers as compared to control mice. This is the first report of such a protective effect from a single dose of rIL-12. Treatment of uninfected mice with rIL-12 induced IFN-gamma mRNA production in their livers. Infection of mice with L. monocytogenes caused a similar increase in IFN-gamma mRNA levels that was not increased further by concurrent treatment with rIL-12. Treatment of mice with an anti-IFN-gamma MAb eliminated the protective effect of IL-12 on Listeria infection. Expression of TNF-alpha, IL-10 and IL-12p40 mRNA in L. monocytogenes-infected mice were not significantly altered by administration of either anti-IL-12 IgG or rIL-12. rIL-12 administration was associated with increased serum AST levels, a measure of liver damage, 1 day after treatment in L. monocytogenes-infected mice. In addition, rIL-12 administration was associated with the increased presence of small inflammatory foci and necrotic hepatocytes in both infected and uninfected mice, suggesting a proinflammatory role for IL-12 in the liver.
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PMID:Recombinant interleukin-12 enhances resistance of mice to Listeria monocytogenes infection. 770 Jan 34

Distinct patterns of T cell cytokine production have been shown to influence the outcome of infection in mouse models and humans. Th1 or Type 1 cytokines, interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) are generally associated with resistance to infection, whereas Th2 or Type 2 cytokines, IL-4 and IL-10 are associated with progressive disease. Leprosy is a useful model for studying the role of cytokines in modulating T cell responses in human infectious disease. Infection by Mycobacterium leprae results in disease manifestations that encompass an immunological spectrum. Tuberculoid patients are able to restrict the growth of the pathogen and mount strong T cell responses to M. leprae. In contrast, lepromatous patients manifest disseminated infection and their T cells weakly respond to M. leprae. We have found that tuberculoid leprosy lesions have a predominance of CD4+ T cells producing the Type 1 cytokine pattern. Secondly, IL-12 mRNA was expressed at 10-fold higher levels in tuberculoid lesions as compared to lepromatous lesions and that IL-12 promotes the selective expansion of the Type 1 cytokine producing cells. In contrast, lepromatous lesions contain CD8+ IL-4-producing cells that suppress antigen-specific T cell responses and promote the outgrowth of additional suppressor T cells. IL-10, also expressed at higher levels in lepromatous as compared to tuberculoid lesions, was found to be produced by macrophages, effectively inhibiting cytokine production and macrophage activity.
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PMID:Cytokine patterns at the site of mycobacterial infection. 771 51

Infection of mice with the protozoan parasite Leishmania major is an established model with which to study the in vivo development of CD4+ Th cell subsets. Interferon-gamma (IFN-gamma), produced by natural killer (NK) cells (AsGM1+, CD4-, CD8-, CD3-), regulates CD4+ T cell subset development and early resistance to L. major. Rapid Th1 cell development and resistance to infection occur in mice that develop an NK cell response early after infection (C3H and immunized BALB/c mice), whereas mice that lack an early NK cell response demonstrate delayed Th1 cell development and enhanced early disease (C57BL/6) or lack detectable Th1 cell development altogether and develop a progressive, fatal infection (BALB/c). Analysis of the requirements for NK cell activation in C3H mice revealed that the NK cell response is both interleukin-2 (IL-2) and IL-12 dependent. Although delayed IL-12 production in C57BL/6 mice precludes NK cell activation, the eventual development of a Th1 response appears to be IL-12 dependent. In contrast, concomitant production of inhibitory factors (IL-4, IL-10, and transforming growth factor beta) with IL-12 and IL-2 prevents NK cell activation in BALB/c mice. Together, these observations support a paradigm of in vivo Th1 cell development that involves IL-12-dependent stimulation of IFN-gamma production by NK cells.
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PMID:The role of the innate immune response in Th1 cell development following Leishmania major infection. 772 8

Infection of mice with the protozoan Leishmania major is an established in vivo model for the definition of factors that contribute to CD4+ T helper cell subset development. In the current study, a central role for IL-12 in directing both the innate and adaptive immune responses to L. major is established. We show that in vivo neutralization of IL-12 eliminates the NK cell cytotoxic response and IFN-gamma production by lymph node cells from 2-day L. major-infected C3H mice. Moreover, anti-IL-12 treatment abrogated Th1 cell development and enhanced Th2 cell development. Consistent with these results, elevated IL-12 p40 production and an increase in the number of IL-12 p40-producing cells were observed within 1 day of infection in C3H mice. Because BALB/c mice lack an early NK cell response or a Th1-type immune response after L. major infection, we investigated the possibility that they had a defect in the ability to produce IL-12. Surprisingly, L. major infection stimulated IL-12 p40 production in BALB/c mice early after infection. Further studies suggest that BALB/c mice are unable to generate an early IFN-gamma response because of the simultaneous production of IL-12 and cytokines that inhibit IL-12 function, such as TGF-beta, IL-4, and IL-10. Together, these data show that IL-12 regulates the immune response to L. major, but that even when IL-12 is induced, Th1 cell development may be interrupted by simultaneous production of inhibitory cytokines.
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PMID:IL-12 is required for natural killer cell activation and subsequent T helper 1 cell development in experimental leishmaniasis. 773 Jun 35

One of the unique features characterizing human tuberculosis (TB) is its pathogenesis. The pathogenesis of TB involves cell-mediated immune responses against Mycobacterium tuberculosis. Concisely, macrophages activated by various soluble mediators or cytokines released through the cellular interactions after infection with M. tuberculosis play a pivotal role in the pathogenesis of human TB. In fact, very complex cellular interactions are going on within the host after infection with or endogenous reactivation of M. tuberculosis. Cells communicate by cell-cell contact and by the release of mediators which may originate locally, called cytokines. In TB infection, macrophages can be activated by two ways; directly with mycobacterial organisms or lipid fractions of their cell walls at the earlier phase of infection, and indirectly with cytokines produced by CD4+ T cells specifically activated by mycobacterial peptide antigens at the later phase of infection. The various clinical features of TB are the summarized outcome of cell to cell interactions mediated by diverse cytokines produced by various immune cells which are initially triggered by M. tuberculosis infection. CD4+ T cells can be classified into two subsets according to the patterns of cytokines they produce; Th1 cells give rise to cell-mediated immunity and are characterized by the production of IL-2 and IFN-gamma, whereas Th2 cells are more efficient in mediating antibody production and secrete IL-4, IL-5, IL-6 and IL-10. Th2 cells can control Th1 cells and vice versa. Th2 cells therefore inhibit the production of cytokines by Th1 cells by releasing IL-4 and IL-10. Infection with mycobacteria stimulates macrophage IL-12 production which appears to act directly on naive CD4+ T cells to induce Th1 development and initiation of cell-mediated immunity. IL-12 is a critical component in the development of cell-mediated immunity. In addition, IL-12 also activates NK cells and gamma/delta T cells, both of which secrete various macrophage-activating factors to kill M. tuberculosis. One of the structural characteristics of M. tuberculosis is the cell wall rich in lipid components. Of importance among various biological activities of the cell wall lipids is the stimulation of mononuclear phagocytes to produce a certain number of cytokines or monokines including IL-12 and IL-10, both of which play important roles in regulation of immune responses in mycobacterial infection and in pathogenesis of TB.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Immunology of tuberculosis and cytokines]. 778 94

Pathogenic bacteria that penetrate the intestinal epithelial barrier stimulate an inflammatory response in the adjacent intestinal mucosa. The present studies asked whether colon epithelial cells can provide signals that are important for the initiation and amplification of an acute mucosal inflammatory response. Infection of monolayers of human colon epithelial cell lines (T84, HT29, Caco-2) with invasive strains of bacteria (Salmonella dublin, Shigella dysenteriae, Yersinia enterocolitica, Listeria monocytogenes, enteroinvasive Escherichia coli) resulted in the coordinate expression and upregulation of a specific array of four proinflammatory cytokines, IL-8, monocyte chemotactic protein-1, GM-CSF, and TNF alpha, as assessed by mRNA levels and cytokine secretion. Expression of the same cytokines was upregulated after TNF alpha or IL-1 stimulation of these cells. In contrast, cytokine gene expression was not altered after infection of colon epithelial cells with noninvasive bacteria or the noninvasive protozoan parasite, G. lamblia. Notably, none of the cell lines expressed mRNA for IL-2, IL-4, IL-5, IL-6, IL-12p40, IFN-gamma, or significant levels of IL-1 or IL-10 in response to the identical stimuli. The coordinate expression of IL-8, MCP-1, GM-CSF and TNF alpha appears to be a general property of human colon epithelial cells since an identical array of cytokines, as well as IL-6, also was expressed by freshly isolated human colon epithelial cells. Since the cytokines expressed in response to bacterial invasion or other proinflammatory agonists have a well documented role in chemotaxis and activation of inflammatory cells, colon epithelial cells appear to be programmed to provide a set of signals for the activation of the mucosal inflammatory response in the earliest phases after microbial invasion.
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PMID:A distinct array of proinflammatory cytokines is expressed in human colon epithelial cells in response to bacterial invasion. 1113 75

Leishmania major are intramacrophage parasites whose eradication requires the induction of T helper 1 (Th1) effector cells capable of activating macrophages to a microbicidal state. Interleukin 12 (IL-12) has been recently identified as a macrophage-derived cytokine capable of mediating Th1 effector cell development, and of markedly enhancing interferon gamma (IFN-gamma) production by T cells and natural killer cells. Infection of macrophages in vitro by promastigotes of L. major caused no induction of IL-12 p40 transcripts, whereas stimulation using heat-killed Listeria or bacterial lipopolysaccharide induced readily detectable IL-12 mRNA. Using a competitor construct to quantitate a number of transcripts, a kinetic analysis of cytokine induction during the first few days of infection by L. major was performed. All strains of mice examined, including susceptible BALB/c and resistant C57BL/6, B10.D2, and C3H/HeN, had the appearance of a CD4+ population in the draining lymph nodes that contained transcripts for IL-2, IL-4, and IFN-gamma (and in some cases, IL-10) that peaked 4 d after infection. In resistant mice, the transcripts for IL-2, IL-4, and IL-10 were subsequently downregulated, whereas in susceptible BALB/c mice, these transcripts were only slightly decreased, and IL-4 continued to be reexpressed at high levels. IL-12 transcripts were first detected in vivo by 7 d after infection, consistent with induction by intracellular amastigotes. Challenge of macrophages in vitro confirmed that amastigotes, in contrast to promastigotes, induced IL-12 p40 mRNA. Reexamination of the cytokine mRNA at 4 d revealed expression of IL-13 in all strains analyzed, suggesting that IL-2 and IL-13 may mediate the IL-12-independent production of IFN-gamma during the first days after infection. Leishmania have evolved to avoid inducing IL-12 from host macrophages during transmission from the insect vector, and cause a striking induction of mRNAs for IL-2, IL-4, IL-10, and IL-13 in CD4+ T cells. Each of these activities may favor survival of the organism.
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PMID:Leishmania promastigotes evade interleukin 12 (IL-12) induction by macrophages and stimulate a broad range of cytokines from CD4+ T cells during initiation of infection. 790 17

The outcome of immune responses critically depends on the pattern of lymphokines secreted by CD4+ T cells. CD4+ T cells may differentiate into interleukin 2 (IL-2) and interferon gamma secreting T helper 1 (Th1)-like cells or IL-4/IL-5/IL-10 secreting Th2-like cells. However, the mechanisms that regulate production of IL-4 or other T cell lymphokines in vivo remain unknown. We use the superantigen, Staphylococcus enterotoxin A (SEA), as a model antigen to characterize the signals that regulate the production of IL-4 in vivo. Induction of IL-4 in normal CD4+ T cells required stimulation with both antigen and IL-4. SEA-specific CD4+ T cells produced large amounts of IL-4 when restimulated within 10 d after in vivo priming. Repetitive application of both signals was required to prevent downregulation of IL-4 production. Although controversy exists regarding the susceptibility of Th2-like cells to tolerogenic signals, high doses of superantigen readily abolished the capacity to produce IL-4 in both naive T cells and in T cells already primed for IL-4 production. Infection with the nematode, Nippostrongylus brasiliensis, reversed the established T cell tolerance, whereas the signals which induced IL-4 production in normal T cells, antigen and IL-4, were not capable of reversing superantigen-specific tolerance in vivo. The major parameter that correlated with the capacity of parasitic infection to break tolerance was magnitude of the lymphoproliferation seen during the course of the infection. The capacity to activate or tolerize the IL-4 pathway in an antigen-specific fashion should prove useful in the design of antigen-specific therapies for autoimmune and allergic diseases.
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PMID:Antigen-specific activation, tolerization, and reactivation of the interleukin 4 pathway in vivo. 791 Aug 42

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