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)

Interleukin-1 (IL-1) -alpha and -beta are potent regulators of inflammatory responses. The naturally occurring interleukin-1 receptor antagonist (IL-1ra) is effective in vitro and in vivo in modulating biological responses to IL-1. We have previously reported the discovery of IL-1 antagonist peptides from the search of phage display libraries. Further characterization of this group of peptides has led to a 15-mer, AF12198, Ac-FEWTPGWYQJYALPL-NH2 (J represents the unnatural amino acid, 2-azetidine-1-carboxylic acid), with both in vitro and in vivo IL-1 antagonist activity. AF12198 selectively binds the human type I IL-1 receptor but not the human type II receptor or the murine type I receptor. In vitro, AF12198 inhibits IL-1-induced IL-8 production by human dermal fibroblasts with a half-maximal inhibition concentration or IC50 of 25 nM and IL-1-induced intercellular adhesion molecule-1 (ICAM-1) expression by endothelial cells with an IC50 of 9 nM. When given as an intravenous infusion to cynomolgus monkeys, AF12198 blocks ex vivo IL-1 induction of IL-6 and down modulates in vivo induction of IL-6. This is the first small molecule to show IL-1 receptor antagonist activity in vivo.
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PMID:AF12198, a novel low molecular weight antagonist, selectively binds the human type I interleukin (IL)-1 receptor and blocks in vivo responses to IL-1. 894 20

The presence of various cytokines, namely hepatocyte growth factor (HGF), interleukin-1 receptor antagonist (IL-1 RA), and interleukins (IL-1 alpha, IL-6, and IL-8), as well as the production of reactive oxygen species (ROS) was investigated in seminal plasma of fertile and infertile patients in order to evaluate the possible value of measuring these substances for the diagnosis of male accessory gland infection, and to assess the possible relationship between oxidative stress and cytokines during leucocytospermia and male accessory gland infection (MAGI). Our findings indicate that all of the measured cytokines seem to be produced locally as well as by white blood cells (WBC) and that, due to the presence of higher numbers of WBC, accessory gland infection may exert a deleterious effect on sperm quality through the production of ROS and/or of particular cytokines such as IL-1 alpha, IL-1 RA, and IL-8. The most specific marker for a sensitivity of 95% in discriminating between cases with or without MAGI is the measurement of IL-6 in seminal plasma. In the absence of WBC several cytokines are constitutively produced and correlate with sperm concentration (HGF, IL-8), alpha-glucosidase (IL-6), and gamma-glutamyltransferase activity (HGF). The measurement of these cytokines in semen may provide clinically useful information for the diagnosis of male accessory gland infection, as well as in the absence of WBC where it can provide information about certain mechanisms of male reproductive function and dysfunction.
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PMID:The relation between reactive oxygen species and cytokines in andrological patients with or without male accessory gland infection. 901 1

Human mast cells readily release a variety of mediators, including cytokines, in response to IgE receptor crosslinking, but the mechanisms governing the expression of cytokines are still unclear. Using a human mast cell line, HMC-1, we show expression of cytokine transcripts as early as 2 h after activation with ionomycin and phorbol myristate acetate (PMA). Resting HMC-1 cells expressed transcripts for interleukin-1 receptor antagonist (IL-1RA), IL-2, IL-4, IL-5, GM-CSF, and weakly for IL-8, and stimulation with ionomycin and PMA induced additional transcripts for IL-6 and IL-13 and upregulated expression of IL-8 transcripts. HMC-1 cells secreted IL-4, IL-8, and GM-CSF protein after activation and dexamethasone significantly inhibited the production of these cytokines. Of significance is the finding that the addition of membranes purified from activated T cells to mast cell cultures induced transcripts selectively for IL-8 and none for other proinflammatory cytokines. Flow cytometry revealed that resting HMC-1 cells express CD40, a molecule involved in contact-dependent signaling of monocytes and B cells by T cells. However, activation of HMC-1 by anti-CD40 antibody did not induce IL-8 gene expression or protein production. This study demonstrates that human mast cells are capable of expressing multiple cytokines that can be inhibited by glucocorticoids. It also raises the possibility that T cells may activate mast cell cytokine synthesis by novel contact-dependent mechanisms. This phenomenon of T cell regulation of mast cell function requires further study.
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PMID:Multifunctional cytokine expression by human mast cells: regulation by T cell membrane contact and glucocorticoids. 908 42

Cytokines play a central role in the modulation of the intestinal immune system. They are produced by lymphocytes (especially T cells of the Th1 and Th2 phenotypes), monocytes, intestinal macrophages, granulocytes, epithelial cells, endothelial cells, and fibroblasts. They have proinflammatory functions [interleukin-1 (IL-1), tumor necrosis factor (TNF), IL-6, IL-8, IL-12] or antiinflammatory functions [interleukin-1 receptor antagonist (IL-1ra), IL-4, IL-10, IL-11, transforming growth factor beta (TGF beta)]. Mucosal and systemic concentrations of many pro- and antiinflammatory cytokines are elevated in inflammatory bowel disease (IBD). An imbalance between proinflammatory and antiinflammatory cytokines was found for the IL-1/IL-1ra ratio in the inflamed mucosa of patients with Crohn's disease, ulcerative colitis, diverticulitis, and infectious colitis. Furthermore, the inhibition of proinflammatory cytokines and the supplementations with antiinflammatory cytokines reduced inflammation in animal models, such as the dextran sulfate colitis (DSS) model, the trinitrobenzene sulfonic acid (TNBS) model, or the genetically engineered model of IL-10 knockout mice. Based on these findings a rationale for cytokine treatment was defined. The first clinical trials using neutralizing monoclonal antibodies against TNF alpha (cA2) or the antiinflammatory cytokine IL-10 have shown promising results. However, many questions must be answered before cytokines can be considered standard therapy for IBD.
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PMID:Cytokines in inflammatory bowel disease. 952 21

A beta2-microglobulin (beta2M) selective adsorbent (Lixelle) for direct hemoperfusion has been used for the treatment of hemodialysis patients with the long-term complication of dialysis related amyloidosis (DRA), but there is no significant correlation between the serum level of beta2M and the occurrence of DRA. Inflammatory cytokines such as interleukin (IL)-1, IL-6, and tumor necrosis factor alpha (TNFalpha) are related to the development of DRA. We studied the adsorptive rates of cytokines in vitro using the Lixelle adsorbent. The adsorptive rates were 98.5% for IL-1beta 98.0% for interleukin-1 receptor antagonist (IL-1RA), 82.9% for IL-6, 99.9% for IL-8, 31.2% for TNFalpha, and 46.1% for soluble TNF receptor (sTNFr), respectively. As the molecular weights of cytokines increase, the adsorptive rates decrease. The Lixelle column adsorbed beta2M and various inflammatory cytokines as well. Therefore, the removal of both beta2M and inflammatory cytokines may play an important role in the treatment of DRA.
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PMID:Lixelle adsorbent to remove inflammatory cytokines. 987

Dissemination of uveal melanomas is almost exclusively haematogenous, making angiogenesis of the tumour a prerequisite for the formation of metastases. Uveal melanomas must employ strategies to evade the immune system in order to escape immune surveillance. We therefore determined the expression of the following angiogenic and immunosuppressive factors in seven human uveal melanoma cell lines using reverse transcriptase-polymerase chain reaction (RT-PCR): secreted interleukin-1 receptor antagonist (sIL-1ra), interleukin (IL)-6, IL-8, IL-10, transforming growth factor (TGF)-alpha, TGFbeta, vascular endothelial growth factor (VEGF), platelet derived growth factor (PDGF), basic fibroblast growth factor (bFGF), angiopoietin-1 and angiopoietin-2. In addition, the secretion of sIL-1ra, IL-6, IL-8, IL-10, TGFbeta and VEGF was assayed by enzyme linked immunosorbent assay (ELISA). The potential of uveal melanoma cell lines to convert plasminogen to angiostatin was tested in an in vitro assay. All the factors except angiopoietin-1 were determined in one or more cell lines using RT-PCR, although these results were not necessarily confirmed by ELISA. Expression of VEGF and angiopoietin-2 was found in all seven cell lines. Production of angiostatin was observed in one cell line. All seven cell lines examined expressed angiogenic factors and most cell lines expressed immunosuppressive factors. The expression of VEGF and angiopoietin-2 in combination with a lack of angiopoietin-1 expression suggest high vascular remodelling capacity and could be of great relevance for the metastatic potential of uveal melanoma.
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PMID:Expression of angiogenic and immunosuppressive factors by uveal melanoma cell lines. 1059 10

Cystic fibrosis (CF) is a genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Despite improvements in treatment, pulmonary disease still remains the primary cause of death among these patients. In order to introduce a normal CFTR gene copy into airway epithelial cells, adenoviral vectors (AV) have been developed. AV are known to induce an inflammatory reaction that limits transgene expression, and can be potentially harmful. No human study has clearly monitored simultaneously, systemic and local inflammatory reaction, during AV administration. We report here the levels of C-reactive protein (CRP), interleukin (IL)-6, IL-8, tumor necrosis factor-alpha (TNF-alpha), and interleukin-1 receptor antagonist (IL-1Ra) in plasma and bronchoalveolar lavage fluid (BALF) from six cystic fibrosis patients receiving AV encoding CFTR (AdCFTR). AdCFTR was administered to three cohorts of two patients into the nose on day 0, at doses ranging from 105 to 4 x 108 plaque-forming units (pfu), followed, on day 1, by aerosolization of 107 to 5.4 x 108 pfu. In order to ensure that patients were in the best clinical condition, and to further attenuate the broncho-pulmonary inflammation secondary to bacterial infection, they received antibiotic therapy, two weeks prior to AdCFTR administration, until 9 to 11 days after. We found that antibiotics markedly decreased CRP, TNF-alpha, IL-6, IL-1Ra levels in blood. In BALF, antibiotics slightly decreased TNF-alpha levels but had no effect on IL-8 and IL-1Ra, while IL-6 levels increased. AdCFTR administration did not induce any systemic or local cytokine release. In both blood and BALF, CRP, IL-8, IL-1Ra, TNF-alpha decreased, while IL-6 levels increased between day -7 and day 3. One patient presented an asymptomatic increase of all parameters in the BALF on day 7. Twenty one days later, he displayed a clinical deterioration suggestive of an exacerbation. In conclusion, this study demonstrates that antibiotic administration tends to attenuate systemic but not local broncho-pulmonary inflammation in CF patients. In the setting of our study, AdCFTR administration did not induce cytokine release. Further studies are necessary to investigate other inflammatory markers and the mechanisms involved during AV-mediated gene transfer for a better understanding of the immune reaction, which continues to hamper the development of gene therapy for CF patients.
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PMID:Cytokine pattern in cystic fibrosis patients during antibiotic therapy and gene therapy using adenoviral vector. 1223 76

The biological activities of IL-18 include its ability to induce the production of inflammatory cytokines such as IL-1 or IL-8 by immunocompetent cells. Our previous study demonstrated that rhIL-18 induces IL-1beta and, to a lesser exted, the secretion of IL-1beta regulatory proteins involving interleukin-1 receptor antagonist (IL-IRa) and soluble interleukin-1 receptor II (sIL-1RII) by neutrophils (PMN), suggesting a significant role of IL-18 in the reactions mediated by IL-1beta. In this study, we estimated the effect of rhIL-18 on the induction of IL-6 and its soluble receptors - sIL-6Ralpha and sgp130 by these cells. Results obtained indicate that IL-18 is a promising candidate for the enhanced secretion of IL-6 by human neutrophils. In contrast, we have not found a significant effect of IL-18 on the release of both soluble receptors of IL-6. The influence of IL-18 on the IL-6 production by PMN appears to indicate a potential role of IL-18 in the early steps of the inflammatory cascade and other immune reactions mediated by IL-6.
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PMID:Effect of IL-18 on the release of IL-6 and its soluble receptors: sIL-6Ralpha and sgp130 by human neutrophils. 1247 76

Proinflammatory cytokines, including interleukin-1 (IL-1) have been implicated in the inflammation that follows corneal alkali injury. The purpose of this series of experiments was to test whether topically applied interleukin-1 receptor antagonist (IL-1ra) could suppress corneal inflammation and promote transparency after alkali injury. Alkali injury was induced on day 0 by application of 1N NaOH to both eyes of Wistar rats (n = 28). Immediately thereafter, eyes received either topical IL-1ra (20 mg ml(-1)) in 0.2% sodium hyaluronate or vehicle alone three times daily during days 0-14. Biomicroscopic features including corneal opacity and neovascularization were assessed using a standard grading scheme. Inflammation was quantified histologically. Corneas excised at day 3 and 7 (randomly selected six eyes in each group per time point studied) were homogenized, and levels of IL-1alpha, IL-1beta, IL-6, IL-8, IL-10, and RANTES were quantified by enzyme-linked immunosorbent assay. Epithelial wound healing was examined by computed analysis of fluorescein stained corneal photographs taken daily until day 14. According to these evaluations, eyes treated with IL-1ra maintained corneal transparency with minimal neovascular invasion. Additionally, corneal damage and cell infiltration were reduced on day 7 (infiltration cells were almost 40% decreased). All cytokine/chemokine levels in IL-1ra treated eyes were significantly lower at day 3, and IL-6 and IL-10 remained significantly lower at day 7 compared to vehicle-treated eyes. IL-1ra treatment retarded epithelial wound healing in the early stage (day 1-4); however, subsequently IL-1ra treated eyes had enhanced healing with full epithelial closure at nearly the same time point as vehicle-treated eyes (day 10). We conclude that local antagonism of IL-1 after alkali injury can significantly decrease corneal inflammation and lead to enhanced corneal transparency.
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PMID:Local suppression of IL-1 by receptor antagonist in the rat model of corneal alkali injury. 1256 3

The objective of the present report was to clarify the postoperative stress response of some inflammatory markers, namely of proinflammatory cytokines and leptin levels during uncomplicated postoperative periods. The results were compared with the dynamics of these parameters during intraabdominal sepsis. We followed 20 patients after a planned resection of colorectal cancer in stage Ib-IV with uncomplicated healing and 13 obese men after laparoscopic non-adjustable gastric banding. These were compared to 12 patients with proven postoperative sepsis. The control group consisted of 18 healthy men. The observed parameters included serum levels of cytokines, tumor necrosis factor-alpha (TNFalpha), interleukin-1 beta (IL-1 beta), interleukin-1 receptor antagonist (IL-1 ra), IL-6, IL-8, soluble receptor of interleukin-2 (sIL-2R) and leptin. It was found that during the first 24 h after resection there was a significant increase in the serum concentration of IL-6 up to 1125+/-240 ng/l, which declined within the next 48-72 h. Serum concentration of TNFalpha was highest 18-24 h after resection (205+/-22 ng/l) and after banding (184+/-77 ng/l). IL-1 beta had a stable serum concentration without significant elevation. Serum concentration of IL-8 after resection rose to 520+/-200 ng/l after 36-48 h. Maximal cytokine levels after gastric banding were quantitatively lower (IL-6 414+/-240 ng/l, TNFalpha 184+/-77 ng/l) than after resection. We found significant elevation of plasma leptin concentration (32+/-10 ng/ml) 24 h after banding compared with preoperative values (18+/-5 ng/ml, p 0.05). Leptin levels 48 and 72 h after banding rapidly returned to the level before operation. During abdominal surgery leptin shows to be an acute phase reactant. Proinflammatory cytokines can be main regulatory factors of leptin during this period. Significant correlation between leptin and TNFalpha (similarly demonstrated by other authors in models of bacterial inflammation) indicates that TNFalpha can be the crucial regulator of leptin generation in the early postoperative period. On the basis of our results we recommend to observe IL-6 and IL-8 at 24-72 h after the surgery in patients with a high risk of early postoperative septic complications.
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PMID:The postoperative stress response and its reflection in cytokine network and leptin plasma levels. 1558 61


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