Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Toxoplasma gondii infection may be clinically silent in immunocompetent individuals but may cause fatal disease in immunocompromised patients such as those with HIV infection. Proinflammatory cytokines are known to be important in murine resistance to T. gondii but there are no data from human models of infection. We have investigated whether phagocytosis of T. gondii, of Mycobacterium tuberculosis (a pathogen which elicits a granulomatous host immune response) and of inert latex particles by THP-1 cells, a human monocytic line, caused gene expression and secretion of tumour necrosis factor (TNF), IL-6 and IL-8. These cytokines are important in recruitment and activation of T lymphocytes, and both TNF and IL-6 may have direct antitoxoplasmacidal and antimycobacterial activity. Phagocytosis of T. gondii by THP-1 cells resulted in minimal gene expression and secretion of TNF, IL-6 and IL-8 similar to that following phagocytosis of inert latex particles. In contrast, phagocytosis of M. tuberculosis resulted in increased gene expression of TNF and IL-8 as well as increased secretion of all three cytokines, particularly IL-8. These observations may partially explain the frequency of non-inflammatory host responses to T. gondii in immunocompetent individuals.
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PMID:Differential cytokine gene expression and secretion after phagocytosis by a human monocytic cell line of Toxoplasma gondii compared with Mycobacterium tuberculosis. 842 93

Despite the importance of tuberculosis as the leading cause of death due to infectious disease in the world, it has only been recently that an understanding of the human host response in this infection has begun to emerge. The key components of this response are cytokines and components of cellular immunity, predominantly T-lymphocytes and macrophages. Though the relationships among the components of the immune response are complex, it seems likely that in response to mycobacterial infection associated with active disease, cytokines such as TNF-alpha and IL-1 beta are produced; these cytokines serve to recruit more lymphocytes, generally of the T(H) (T helper) phenotype, which then produces substances such as the macrophage activating factor interferon-gamma. Macrophages activated by IFN-gamma ar thus stimulating to enhance intracellular killing of mycobacteria. The role of other cytokines, such as IL-6 and IL-8, both of which are induced by M. tuberculosis or its cell was components, is less clear. Further elucidation of the human host response to tuberculosis should help in the development of new vaccines and treatment strategies.
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PMID:Human host response to Mycobacterium tuberculosis. 852 36

Phagocytosed M. tuberculosis either multiply inside the endocytic compartment of mononuclear phagocytes or they are destroyed by the host cell. Due to this macrophage-shelter (ab)used by mycobacteria, tuberculosis is controlled by the cellular immune response. Protection against mycobacteria depends on alpha/beta T-cells expressing the CD4 or CD8 phenotype. T-cell-mediated immunity amplifies macrophage capacities to kill and digest the bacilli. Specific alpha/beta T-cells produce several cytokines that attract and activate macrophages and additional lymphocytes, such as: interferon-gamma (IFN-gamma) which has the capacity to activate several antimicrobial properties of macrophages; tumour necrosis factor-alpha (TNF-alpha) a key cytokine involved in granuloma formation; interleukins 2, 6 and 8 (IL-2; IL-6 and IL-8); and interleukin 12 (IL-12), a candidate cytokine for the induction of Th1 cells. Furthermore, CD4+ and CD8+ T-cells display cytotoxic activity, which permits them to control mycobacterial growth through destruction of the infected cells. Escaping bacteria are subsequently ingested and destroyed by surrounding macrophages activated by T-cells. There is evidence to associate gamma/delta T-cells with antimycobacterial immunity, such as their preferential accumulation in inflammatory lesions, in necrotic areas of tuberculous lymphadenitis, and potent in vitro stimulation by M. tuberculosis components. In addition, M. tuberculosis activated gamma/delta T-cells are cytolytic and secrete several cytokines. Hence, clinical tuberculosis is associated with T-cell reactivity which controls the local concentrations of tubercle bacilli. Taken together, the cellular response, cytokine regulation, and the definition of target molecules are important aspects for the understanding of pathological immune mechanisms in tuberculosis.
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PMID:Functions of T-cell subsets and cytokines in mycobacterial infections. 859 May 67

The host response to Mycobacterium tuberculosis is dependent on the accumulation and activation of cytotoxic and memory CD4+ T cells, resulting in granuloma formation and delayed type hypersensitivity. We characterized the cellular response of radiographically involved lung segments from 17 HIV-positive and 11 HIV-negative patients with acute tuberculosis (TB) using bronchoalveolar lavage (BAL) and compared the response to uninvolved segments, normal control subjects and peripheral blood. In both HIV-positive and HIV-negative patients, radiographically involved segments had significantly increased numbers of total cells per milliliter, percent of neutrophils recovered, and percent of lymphocytes recovered compared with uninvolved segments or normal control subjects, but HIV-positive patients had a lower proportion of lymphocytes in the involved segments than HIV-negative patients with tuberculosis (19 +/- 5% versus 33 +/- 5%; p < 0.05). Lymphocyte subset analysis demonstrated that HIV-positive patients had markedly reduced percentages of CD4+ lymphocytes (CD4+ lymphocytes in HIV-positive TB involved site 25 +/- 6%; HIV-negative TB involved site 73 +/- 2%; p < 0.01) and an increase in the percentage of CD8+ lymphocytes (HIV positive involved site 61 +/- 6% versus HIV negative involved site 19 +/- 3%; p < 0.01). Immunohistochemistry of lung biopsy tissue in five HIV-negative patients showed similar lymphocyte subset profiles as BAL, indicating that BAL reflects cell populations in tissue granulomas. BAL lymphocytes from four HIV-positive and four HIV-negative tuberculosis patients demonstrated immune activation by staining with a murine antibody to TIA-1, a cytoplasmic protein associated with cytotoxicity and apoptosis (HIV positive 48 +/- 6%, HIV negative 31 +/- 7%, normals 11 +/- 5%). Steady state mRNA for gamma-interferon was decreased in four HIV-positive patients when compared with four HIV-negative patients. IL-8 production was comparable in HIV-negative and HIV-positive patients with focal disease but reduced in two patients with miliary tuberculosis. We conclude that HIV-positive patients with+ tuberculosis have a reduced enrichment and activation of immune cells in the lung, and this failure of a CD4+ alveolitis limits an effective immune response.
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PMID:Tuberculosis in HIV-positive patients: cellular response and immune activation in the lung. 861 69

The human immune response to tuberculosis is partly mediated by the proinflammatory cytokines tumour necrosis factor (TNF), interleukin (IL)-6, and IL-8. We investigated plasma concentrations of these cytokines before and after maximal lipopolysaccharide stimulation ex vivo of whole blood leucocytes from Zambian patients. 32 patients with non-fatal tuberculosis, 25 of whom were seropositive for human immunodeficiency virus (HIV), were followed for 9 months. Patients were assessed at presentation to hospital (visit A), after 2 months' antimycobacterial therapy (visit B), and when chemotherapy was completed (visit C). Between visits A and B, patients regained weight (P = 0.03) and became less anaemic (P = 0.0001). At visit B, haemoglobin concentration remained lower in HIV seropositive patients (P = 0.001) and the erythrocyte sedimentation rate (ESR), initially elevated in all patients, was higher in HIV seropositive patients (100 +/- 6 mm vs. 43 +/- 11 mm in 1 h in seronegative patients; P = 0.002). Plasma IL-8 concentrations were increased at visit C as was IL-8 secretion ex vivo (P < 0.0001 at all time points). Otherwise plasma cytokine levels and secretion ex vivo remained similar throughout the study. Concurrent HIV infection resulted in persistently decreased IL-6 secretions ex vivo although ESR remained high. In summary, after antibiotic therapy in vivo IL-8 secretion ex vivo increased, which supports other data suggesting that IL-8 has a role in immunity to tuberculosis.
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PMID:Cytokine secretion in vivo and ex vivo following chemotherapy of Mycobacterium tuberculosis infection. 876 91

Our study investigated the presence of IL-8 in pleural exudates from tuberculosis patients (TBP) (n = 13), and evaluated whether it was related with the profile of major immunocompetent cells present in their pleural and peripheral compartments. To allow comparisons, an additional group of patients with parapneumonic pleural effusions (PNE) (n = 7) was included. Blood peripheral immunophenotypic studies were also carried out in 12 age-matched healthy controls (Co), and 39 tuberculosis patients classified, according to the extent of pulmonary involvement, into mild (n = 9), and advanced (n = 30) cases. Patients were recruited before starting therapy, had HIV negative serology, and showed no age differences among groups (mean +/- SD., 40.7 +/- 14.7 years). IL-8 concentrations were measured by an ELISA method while immunophenotypic analysis was performed by using FITC-conjugated monoclonal antibodies reacting against the following cell surface molecules: CD3, CD4, CD8, CD25 (IL-2R+ cells), CD19, and CD68. IL-8 was detected in all pleural exudates though levels in the TB patients, 384 +/- 110 pg/ml, appeared significantly higher than the PNE group, 185 +/- 110 pg/mg, (P < 0.015, mean +/- S.D.). In turn, the former group presented values of pleural CD3+, CD4+, and CD25, which were found increased in comparison with PNE patients (P < 0.01). Unlike the pleural compartment, patients with TBP showed a marked and significant decrease in their circulating levels of cells bearing the CD3, CD4, CD19, CD25, and CD68 phenotypes not only when comparing with Co but also with PNE and mild patients. Differences between the levels of pleural and peripheral T-cells from TBP patients may be the reflection of an important influx of T-lymphocytes from the circulatory system to the pleural cavity, probably linked to the presence of chemotactic factors within the pleural fluid like IL-8.
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PMID:Levels of interleukin-8 in tuberculous pleurisy and the profile of immunocompetent cells in pleural and peripheral compartments. 909 79

Cytokines play an important role in granuloma formation, but the extent that cytokine profiles are similar in different granulomatous diseases and whether differences in the histopathologic features of the granulomatous response results from differences in cytokine production have not been evaluated. To investigate these questions, we used RT-PCR to quantify the expression of mRNAs coding for 16 cytokines in granulomatous lymph nodes from patients with tuberculosis and sarcoidosis and from control tissues, and we sought correlations between the level of expression of these cytokines and the histopathologic features of the granulomas. Expression of mRNAs coding for a number of cytokines (IL-1beta, IFN-gamma, TNF-alpha, granulocyte-macrophage (GM)-CSF, IL-12 (p40), and lymphotoxin-beta) was increased in tuberculous and sarcoid granulomas compared with that of control tissues. All sarcoid granulomas were shown to express a Th1 pattern of cytokine mRNAs, while tuberculous lymph nodes expressed either a Th1 or a Th0 profile. GM-CSF and lymphotoxin-beta mRNAs were more abundant in sarcoid than in tuberculous granulomas, whereas IL-8 mRNA was strongly expressed only in tuberculous lymph nodes. Strong expression of GM-CSF, TNF-alpha, and IL-8 by granulomas was shown to be correlated, respectively, with the presence of florid granulomatous lesions, the absence of central necrosis, and the presence of neutrophil infiltration. These results demonstrate that the formation of tuberculous and sarcoid granulomas in humans is associated with the expression of characteristic cytokine profiles and indicate that the expression of certain cytokines is associated with the development of specific pathologic features in the resulting granulomas.
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PMID:Cytokine patterns in tuberculous and sarcoid granulomas: correlations with histopathologic features of the granulomatous response. 930 Jul 29

Blood monocytes from patients with active tuberculosis are activated in vivo, as evidenced by an increase in the stimulated release of proinflammatory cytokines, such as TNF-alpha, and the spontaneous expression of IL-2R. Further, monocytes from patients demonstrate an augmented susceptibility to a productive infection with HIV-1 in vitro. Mycobacterium tuberculosis and its components are strong signals to activate monocytes to production of cytokines. In this study we examined the basis of activation of monocytes during active tuberculosis and by M. tuberculosis. We found a constitutive degradation of I kappa B-alpha, the major cytoplasmic inhibitor of nuclear factor kappa B (NF-kappa B), in freshly isolated PBMC and monocytes from patients with tuberculosis. In contrast, I kappa B-alpha levels in PBMC and monocytes from healthy subjects or from patients with nontuberculous pulmonary conditions were intact. Further, by electrophoretic mobility shift assay, NF-kappa B was activated in monocytes from tuberculous patients. The expression of I kappa B-alpha gene, which is responsive to activation by NF-kappa B, was up-regulated in PBMC and monocytes from patients, but not in mononuclear cells from healthy subjects or those with nontuberculous lung diseases. By contrast, the expression of other adherence-associated early genes, such as IL-8 and IL-1 beta, was not up-regulated in PBMC of tuberculous patients. Further, M. tuberculosis and its tuberculin, purified protein derivative, induced the degradation of I kappa B-alpha and the expression of I kappa B-alpha mRNA, and purified protein derivative induced the activation of NF-kappa B in monocytes.
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PMID:Regulation of nuclear factor-kappa B and its inhibitor I kappa B-alpha/MAD-3 in monocytes by Mycobacterium tuberculosis and during human tuberculosis. 937 2

Increased levels of interleukin-6 (IL-6) and IL-8 are found in various immunologically mediated inflammatory disorders. Concentrations of IL-6, IL-8 and the soluble form of the IL-6 receptor (sIL-6R) were determined in serum and effusion fluid of 25 patients with tuberculous pleurisy utilizing enzyme linked immunosorbent assays (EIA). Serum IL-6 levels were only slightly increased in patients with tuberculous pleurisy in comparison to controls (11.1 +/- 2.1 vs 7.3 +/- 1.0 pg ml-1). IL-8 could not be detected in the serum of tuberculosis patients, but it was detected in the serum of healthy controls (8.0 +/- 1.5 pg ml-1). In comparison to serum, IL-6 and IL-8 were found in high concentrations in pleural effusions (IL-6: 932 +/- 70 vs 11.1 +/- 2.1 pg ml-1, P < 0.0001; IL-8: 450 +/- 85 vs 0 +/- 0 pg ml-1). In contrast, sIL-6R concentrations were much higher in serum compared to pleural effusion levels [30,477 +/- 1905 vs 9881 +/- 1177 pg ml-1, P < 0.0001 (mean +/- SEM)]. The authors conclude that elevated levels of IL-6 and IL-8 in pleural effusions are compartmentalized at the site of active disease. The low levels of sIL-6R in the presence of high levels of IL-6 in pleural effusions, and the high levels of sIL-6R in the presence of low levels of IL-6 in serum suggest that the expression or shedding of sIL-6R may be downregulated in the presence of excessive amounts of IL-6.
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PMID:Compartmentalization of pro-inflammatory cytokines in tuberculous pleurisy. 951 18

To our knowledge, this is the first sequential study of cytokines in tissue sections of developing and healing tuberculous (BCG) lesions. In situ hybridization, immunohistochemical, and RT-PCR techniques were used. Cytokine mRNAs showed a biphasic pattern. The percentage of mononuclear cells (MN) containing IL-1beta, TNF-alpha, MCP-1, and IL-8 mRNAs was highest in 1- to 3-day lesions, apparently because of the nonspecific inflammatory response caused by the tubercle bacilli in the BCG vaccine. At 5 days, this percentage was significantly reduced. With IFN-gamma, the peak and trough were delayed by 2 days. By 9 days, the percentage of MN containing the mRNAs of all five cytokines had again increased and the rabbits had become tuberculin-positive. In general, MCP-1 and TNF-alpha proteins and the vascular adhesion molecules, ICAM, VCAM, and perhaps ELAM, peaked at about 3 days. Many mononuclear cells surrounding the central areas of solid and liquefied caseous necrosis contained chemokine IL-8 mRNA. IL-8 is known to attract PMN, and PMN were present nearby. In contrast, MN containing chemokine MCP-1 mRNA were present more peripherally in areas rich in macrophages and lymphocytes. The early nonspecific cytokine response seems to be an adjuvant effect of the mycobacteria in BCG vaccine in that it causes a rapid entry of macrophages, lymphocytes, granulocytes, and probably dendritic cells into local sites of antigen deposition. This effect should be considered in developing improved vaccines for the prevention of tuberculosis, because BCG vaccines producing a strong early cytokine response should be more immunogenic than BCG vaccines with similar antigens producing a weak response.
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PMID:Nonspecific and immune-specific up-regulation of cytokines in rabbit dermal tuberculous (BCG) lesions. 954 73


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