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)

The presence and the role of interleukin 10 (IL-10), a potent cytokine synthesis inhibitory factor and antiinflammatory cytokine, were investigated in rheumatoid arthritis (RA). The expression of both mRNA and protein for IL-10 could be demonstrated in RA and osteoarthritis (OA) joints. Human IL-10 mRNA could be demonstrated by polymerase chain reaction amplification of cDNA made by reverse transcription of total RNA extracted directly from synovial tissue in five out of five RA and four out of five OA patients. IL-10 protein was demonstrated by specific immunoassay and immunohistology. IL-10 protein was spontaneously produced in all 11 RA and 17 OA synovial membrane cultures investigated, and this production was sustained for up to 5 d in culture in the absence of any extrinsic stimulation. IL-10 protein could also be detected by immunohistology in all five RA and four OA synovial membrane biopsies investigated, but not three normal synovial membranes. Immunohistology revealed that the IL-10 was localized to the synovial membrane lining layer and mononuclear cell aggregates. Immunofluorescence double staining revealed that the sources of IL-10 were monocytes in the lining layer, and T cells in the mononuclear cell aggregates. We found evidence that the IL-10 expression was functionally relevant, as neutralization of endogenously produced IL-10 in the RA synovial membrane cultures resulted in a two- to threefold increase in the protein levels of proinflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and IL-1 beta, although IL-6 and IL-8 levels were not affected. The addition of exogenous recombinant IL-10 to the RA synovial membrane cultures resulted in a two- to threefold decrease in the levels of TNF-alpha and IL-1 beta. IL-8 levels were reduced by day 5; however, IL-6 levels were not affected by exogenous IL-10. Neutralization of the endogenous IL-10 in two out of seven RA synovial membrane cultures resulted in the expression of detectable levels of interferon gamma (561-1,050 pg/ml). Taken together, the above findings suggest that IL-10 is spontaneously produced in RA and OA and is an important immunoregulatory component in the cytokine network of RA, regulating monocyte and in some cases T cell cytokine production.
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PMID:Immunoregulatory role of interleukin 10 in rheumatoid arthritis. 816 35

Psoralen plus UV-A (PUVA) is an effective therapy for psoriasis but also for other inflammatory dermatoses. The precise mechanisms of action, however, are not absolutely clear. Therefore, the effect of PUVA on the release of the proinflammatory cytokines interleukin (IL)-1, IL-6, IL-8 and tumor necrosis factor alpha (TNF alpha) was studied. Peripheral blood mononuclear cells (PBMC) obtained from humans were incubated with 8-methoxypsoralen (8-MOP) and exposed to UV-A (20 kJ/m2). This treatment resulted in a significant reduction of IL-6 and IL-8 amounts in the supernatants. In addition, an inhibition of IL-1 beta and TNF alpha production by lipopolysaccharide (LPS)-stimulated PBMC was observed upon PUVA treatment. Accordingly, northern blot analysis showed decreased levels of mRNA encoding for IL-1 beta, IL-6, IL-8 and TNF alpha in PUVA-treated PBMC. Finally PBMC were obtained from psoriatics undergoing oral photochemotherapy before the beginning and after completion of treatment. The PBMC collected after PUVA spontaneously produced significantly less IL-6 and IL-8 in comparison to the respective samples obtained before therapy. A similar suppression of IL-1 beta and TNF alpha by in vivo PUVA was found in LPS-stimulated PBMC. The present data demonstrate that PUVA both in vitro and in vivo suppresses the production of the proinflammatory cytokines IL-1 beta, IL-6, IL-8 and TNF alpha by PBMC. Because these cytokines are important in the mediation of inflammatory reactions, one may speculate that the inhibitory effects could contribute to the antiinflammatory activity of PUVA.
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PMID:Cytokine release by peripheral blood mononuclear cells is affected by 8-methoxypsoralen plus UV-A. 816 38

To explore the pathogenic mechanisms involved in adenovirus infection, we evaluated total levels of immunoglobulins, antiadenovirus antibodies, adenovirus-specific circulating immune complexes, and cytokines in serum samples obtained from 38 hospitalized children with adenovirus infection. According to their clinical findings and outcome, the infections were classified as follows: (1) moderate (group I, n = 10), (2) severe (group II, n = 12), and (3) fatal (group III, n = 16). About 60% of the children had elevated IgM levels. IgG-containing adenovirus-specific circulating immune complexes were initially detected in 7 of 16 group III patients, 4 of whom had low serum levels of the third component of complement. A decrease in initial antiadenovirus IgG antibodies was observed in 3 of 10 patients in group III. Serum interleukin-6 was not detected in group I (none of 10), but was present in group II (7 of 12, p = 0.016) and group III (13 of 16, p < 0.001). Interleukin-8 was detected in all groups; values in fatal cases were significantly higher than in surviving children. Tumor necrosis factor alpha was not observed in group I (none of 10) and was uncommon in group II (2 of 12) but was frequently detected in group III (9 of 15, p = 0.01). Interleukin-1 and interleukin-4 were rarely detected in serum samples. Increased concentrations of interleukin-6, interleukin-8, and tumor necrosis factor alpha were associated with hypoperfusion, febrile peaks, tonic-clonic seizures, and septic shock. In 5 of 10 patients in groups II and III, autoantibodies specific for smooth muscle were found. Our findings indicate that high serum values for interleukin-6, interleukin-8, and tumor necrosis factor alpha are associated with severity of adenovirus infection.
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PMID:Cytokines in adenoviral disease in children: association of interleukin-6, interleukin-8, and tumor necrosis factor alpha levels with clinical outcome. 817 57

Antibiotic-induced endotoxin (lipopolysaccharide; LPS) release may precipitate septic shock. In the present study the effect of teicoplanin, which has been reported to neutralize LPS in experimental models, on LPS neutralization was investigated in human whole blood samples. Levels of interleukin 8, a preinflammatory cytokine which was stimulated by Salmonella minnesota R595 LPS (12.6 micrograms/ml), were monitored over time. Interleukin 8 concentrations increased over time up to 24 h. When LPS was preincubated with teicoplanin (antibiotic: LPS ratio 20:1, w/w), interleukin 8 concentrations were found significantly (p < 0.05) reduced at 4, 8 and 24 h after LPS challenge. Interleukin 1 beta (at 4, 8 and 24 h) and tumor necrosis factor alpha (at 8 and 24 h) levels were also significantly decreased by teicoplanin. In this experiment model, a teicoplanin:LPS ratio 100-fold less than the ratio achievable in plasma of septic shock patients was able to reduce interleukin 8, which has been correlated with the severity of septic disease.
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PMID:Inhibition of endotoxin-induced interleukin 8 release by teicoplanin in human whole blood. 818 90

Cytokines such as tumor necrosis factor alpha (TNF-alpha), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 8 (IL-8), IL-6, IL-1 alpha, and IL-1 beta produced during the immune and inflammatory responses to bacterial stimuli have been reported to interact with polymorphonuclear neutrophil (PMN) activities. However, contradictory findings on their direct and priming effects on the PMN oxidative burst, which is essential for bacterial killing, have been reported. We have used a flow cytometry method to study the effects of these cytokines on the oxidative burst of PMN in whole blood to avoid PMN activation related to isolation procedures. None of the cytokines tested directly activated the PMN oxidative burst, but they did have differential priming effects on the oxidative burst in response to bacterial N-formyl peptides. TNF, GM-CSF, and IL-8 strongly primed a subpopulation of PMN to produce H2O2 in response to N-formyl-methionyl-leucyl-phenylalanine (FMLP), while IL-1 alpha, IL-1 beta, and IL-6 failed to do so. Furthermore, the addition of TNF, GM-CSF, or IL-8 to whole blood increased the capacity of a subpopulation of PMN to bind N-formyl peptides, a phenomenon that could account, at least in part, for the strong H2O2 production in response to FMLP after priming by the cytokines. The size of the primed hyperresponsive subpopulation was greater after priming with TNF or GM-CSF than after priming with IL-8. However, GM-CSF, TNF, and IL-8 at suboptimal concentrations cooperated in the induction of a subpopulation hyperresponsive to FMLP. These results show that, of the various proinflammatory cytokines tested, TNF, GM-CSF, and IL-8 strongly prime the PMN oxidative burst in response to bacterial peptides in whole blood and suggest that these cytokines may play a critical role in bacterial killing in vivo.
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PMID:Differential priming effects of proinflammatory cytokines on human neutrophil oxidative burst in response to bacterial N-formyl peptides. 818 40

This study compared the cytokine production of uroepithelial cell lines in response to gram-negative bacteria and inflammatory cytokines. Human kidney (A498) and bladder (J82) epithelial cell lines were stimulated with either Escherichia coli Hu734, interleukin 1 alpha (IL-1 alpha), or tumor necrosis factor alpha (TNF-alpha). Supernatant samples were removed, and the RNA was extracted from cells at 0, 2, 6, and 24 h. The secreted cytokine levels were determined by bioassay or immunoassay; mRNA was examined by reverse transcription-PCR. The two cell lines secreted IL-6 and IL-8 constitutively. IL-6 and IL-8 mRNA were constitutively produced in both cell lines; IL-1 beta mRNA was detected in J82 cells. IL-1 alpha induced significantly higher levels of IL-6 secretion than did E. coli Hu734 or TNF-alpha. IL-1 alpha and TNF-alpha induced significantly higher levels of IL-8 secretion than did E. coli Hu734. Secreted IL-1 beta was not detected; IL-1 alpha and TNF-alpha were not detected above the levels used for stimulation. IL-1 alpha, IL-1 beta, IL-6, and IL-8 mRNAs were detected in both cell lines after exposure to the stimulants. TNF-alpha mRNA was occasionally detected in the J82 cell line after TNF-alpha stimulation. Cytokine (IL-6 and IL-8) and control (glyceraldehyde 3-phosphate dehydrogenase [G3PDH] and beta-actin) mRNA concentrations were quantitated with internal PCR standards. Cytokine mRNA levels relative to beta-actin mRNA levels were the highest in E. coli-stimulated cells. In comparison, the cytokine mRNA levels relative to G3PDH mRNA levels were the highest in IL-1 alpha-stimulated cells. beta-Actin mRNA levels decreased after bacterial stimulation but not after cytokine stimulation, while G3PDH mRNA levels increased in response to all of the stimulants tested. These results suggested that E. coli Hu734 lowered the beta-actin mRNA levels in uroepithelial cells, thus distorting the IL-6 and IL-8 mRNA levels relative to this control. In summary, E. coli IL-1 alpha and TNF-alpha were found to activate the de novo synthesis and secretion of IL-6 and IL-8 in uroepithelial cells. These results emphasize the role of epithelial cells in cytokine-mediated responses during the early stages of infection.
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PMID:Uroepithelial cells are part of a mucosal cytokine network. 818 54

Multiorgan dysfunction still occurs after cardiopulmonary bypass and remains a major cause of morbidity and mortality, especially in the pediatric age group. This is consequent upon the so-called systemic inflammatory response to bypass with an increase in inflammatory mediators. Hemofiltration may be able to attenuate the effects of this response by elimination of some or all of these mediators. We undertook a prospective, randomized study to investigate the effect of hemofiltration on plasma levels of the cytokines tumor necrosis factor alpha, interleukin-8, and interleukin 6 in 18 infants and children undergoing deep hypothermic bypass. Serial plasma samples were taken before, during, and after bypass. Assay of the plasma samples revealed presence of the cytokines in a number of subjects in both groups, in some cases before operation. There were significant reductions in levels of tumor necrosis factor after hemofiltration, with no reduction noted in the group not undergoing hemofiltration. A similar difference (p < 0.05) was detected in the levels of interleukin-6 between the two groups after bypass, although this was largely due to changes in 2 subjects. Interleukin-8 was detected in a small number of subjects insufficient for statistical analysis, but with higher values in the group undergoing hemofiltration. We conclude that hemofiltration has the potential to remove cytokines from the circulation, with consequent beneficial effects.
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PMID:Cytokine production and hemofiltration in children undergoing cardiopulmonary bypass. 826 78

This study was performed to examine the in vivo effects of a bolus of recombinant human growth hormone (r-hGH) on the human immune system. In a double blind placebo controlled cross over study, healthy volunteers were given 2 IU r-hGH as an intravenous infusion. r-hGH did not influence the subpopulations of blood mononuclear cells (BMNC), natural killer cell activity, in vitro proliferative responses or production of interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-2, IL-6, IL-8, tumor necrosis factor alpha (TNF alpha), TNF beta or interferon gamma in supernatants from BMNC stimulated with either lipopolysaccharide or phytohemagglutinin. However, two h after infusion a significant neutrocytosis occurred. It is concluded that a bolus infusion of r-hGH to healthy volunteers exerts only minor effects on the human immune system.
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PMID:Effects of an acute bolus growth hormone infusion on the human immune system. 828 61

Interleukin-8 (IL-8), a chemotactic cytokine for T lymphocytes and neutrophils, is induced in several cell types by a variety of stimuli including the inflammatory cytokines IL-1 and tumor necrosis factor alpha TNF-alpha. Several cis elements, including a binding site for the inducible transcription factor NF-kappa B, have been identified in the regulatory region of the IL-8 gene. We have examined the ability of various NF-kappa B subunits to bind to, and activate transcription from, the IL-8 promoter. A nuclear complex was induced in phorbol myristate acetate-treated Jurkat T cells which bound specifically to the kappa B site of the IL-8 promoter and was inhibited by addition of purified I kappa B alpha to the reaction mixture. Only antibody to RelA (p65), but not to NFKB1 (p50), NFKB2 (p50B), c-Rel, or RelB was able to abolish binding, suggesting that RelA is a major component in these kappa B binding complexes. Gel mobility shift analysis with in vitro-translated and purified proteins indicated that whereas the kappa B element in the human immunodeficiency virus type 1 long terminal repeat bound to all members of the kappa B/Rel family examined, the IL-8 kappa B site bound only to RelA and to c-Rel and NFKB2 homodimers, but not to NFKB1 homodimers or heterodimers of NFKB1-RelA. Transient transfection analysis demonstrated a kappa B-dependent expression of the IL-8 promoter in a human fibrosarcoma cell line (8387) and in Jurkat T lymphocytes. Cotransfection with various NF-kappa B subunits indicated that RelA and c-Rel, but neither NFKB1 nor heterodimeric NFKB1-RelA, was able to activate transcription from the IL-8 promoter. Furthermore, cotransfection of NFKB1 and RelA, although able to support activation from the human immunodeficiency virus type 1 long terminal repeat, failed to activate expression from the IL-8 promoter. Antisense oligonucleotides to RelA, but not NFKB1, inhibited phorbol myristate acetate-induced IL-8 production in Jurkat T lymphocytes. These data demonstrate the differential ability of members of the kappa B/Rel family to bind to, and activate transcription from, the IL-8 promoter. Furthermore, while providing a novel example of a kappa B-regulated promoter in which the classical NF-kappa B complex is unable to activate transcription from the kappa B element, these data provide direct evidence for the role of RelA in regulation of IL-8 gene expression.
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PMID:NF-kappa B subunit-specific regulation of the interleukin-8 promoter. 841 15

This study compared the repertoire of cytokines produced by epithelial cell lines and human peripheral blood monocytes in response to Escherichia coli. The A-498 and J82 urinary tract epithelial cell lines and human peripheral blood monocytes were exposed to E. coli Hu734. The cytokine content of single cells was detected by indirect immunofluorescence using monoclonal antibodies to interleukin-1 alpha (IL-1 alpha), IL-1 beta, tumor necrosis factor alpha (TNF-alpha), TNF-beta, IL-6, IL-8, and granulocyte macrophage-colony-stimulating factor, and the number of positive cells was used to quantitate the response. The J82 bladder cell line stained positive for IL-6, IL-8, and IL-1 alpha. The IL-8 and IL-6 response peaked at 2 h, while the number of IL-1 alpha-positive cells reached a peak 6 h after E. coli stimulation. The A-498 kidney cell line stained for IL-8 with a peak at 2 h and IL-6 with a peak at 6 h after E. coli stimulation. Peripheral blood monocytes stained for the cytokines IL-1 alpha, IL-1 beta, IL-8, IL-6, and TNF-alpha but not for TNF-beta and granulocyte macrophage-colony-stimulating factor after stimulation with E. coli. The results demonstrated that bacteria activated a cytokine response in the epithelial cell lines and monocytes. The epithelial cell lines had a more limited cytokine response profile than circulating monocytes, which may serve to limit the consequences of microbial exposure at the mucosal surface and help maintain the integrity of other tissue compartments.
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PMID:Selective cytokine production by epithelial cells following exposure to Escherichia coli. 842 89


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