UNIPROT:P10145 - FACTA Search

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Query: UNIPROT:P10145 (IL-8)
23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Whatever initiates inflammation, the final message mediating cellular invasion is chemical. This consideration allows rational development of anti-inflammatory treatments. Two main classes of chemotactic mediator are recognised. Water-soluble peptides, e.g. cytokines derived from macrophages and other cells, play an important integrating part in the early recruitment of neutrophils and mononuclear cells, and in the amplification of immune responses. Lipid-soluble mediators, of which leukotriene B4 is the most highly chemotactic for neutrophils, are important in secondary amplification. In inflammatory bowel disease, we have shown evidence of increased synthesis of cytokines interleukin 1, 6 and 8. These are associated with activation of circulating monocytes in active Crohn's disease, of lamina propria macrophages in relapse of both ulcerative colitis and Crohn's disease, and development of adhesion molecules on vascular endothelium. Our studies show that interleukin 6 is selectively increased in Crohn's disease, whilst preliminary findings suggest that enhanced synthesis of interleukin 8 is particularly characteristic of ulcerative colitis. Patterns of cytokine synthesis may, therefore, be of diagnostic value. They also offer the potential for therapeutic strategies since cytokine antagonists are becoming available. We have also demonstrated increased synthesis of leukotrienes in active inflammatory bowel disease. Since leukotriene B4 is quantitatively the main chemotactic signal in the mucosa in inflammatory bowel disease during relapse, we investigated the therapeutic effect of suppressing leukotriene B4 synthesis by treating patients with fish oil (as Hi-EPA), giving 4.5 g daily of eicosapentaenoic acid. This competes for the 5-lipoxygenase enzymes, inhibiting leukotriene B4 and promoting synthesis of the less chemotactic product, LTB5.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Therapeutic interventions in gastrointestinal disease based on an understanding of inflammatory mediators. 135 43

Interleukin-1 (IL-1) is a 17-kDa pro-inflammatory cytokine synthesized from a variety of cell types primarily in association with disease states or during host perturbation such as immune responses. At pM or even fM concentrations, IL-1 triggers various responses in nearly all cells. It appears that there is little or no major role for IL-1 in homoeostatic mechanisms. There are two IL-1's (alpha and beta) each with its distinct sequence; there are two IL-1 receptors. Disease states such as local and systemic infection, septic shock, degenerative arthritis and autoimmune diseases such as nephritis, vasculitis and inflammatory bowel disease appear to be mediated, in part, by IL-1. Organ failure, capillary leak and death occur in animals after a combination of tumour necrosis factor (TNF) and IL-1 which is more effective in inducing these changes than either cytokine alone. IL-1 is also a potent inducer of endothelial cell adhesion molecules, IL-6, and IL-8, a neutrophil chemotactic and activating factor. Strategies for reducing the effects of IL-1 have been based on suppression of transcription, translation, or secretion; more recently, receptor blockade has been a new approach. A naturally occurring IL-1-specific receptor antagonist (IL-1ra), which shares 40% conserved amino-acid homology with IL-1 beta, binds to IL-1 surface receptors with the same affinity as IL-1 but does not possess agonist activity and acts as a competitive inhibitor of IL-1. Studies using the IL-1ra to block endogenous IL-1 in a variety of animal disease models suggest that IL-1 plays a key role in triggering the cascade of inflammatory responses. In addition, the IL-1ra reduces the spontaneous production of growth factors and proliferation of leukaemic cells. The IL-1ra may be an advantageous therapy in patients with sepsis, diabetes, inflammatory bowel, arthritis and cancer.
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PMID:Reduction of inflammation by decreasing production of interleukin-1 or by specific receptor antagonism. 139 23

The mucosal immune system consists of a number of compartments that are populated with a different assortment of cells and serve different functions. The cytokines produced by the cells in each of these compartments are currently being defined. This is best understood in relation to B cells, whose proliferation and maturation is guided by a sequence of cytokines. PP are inductive sites that preferentially stimulate IgA production. At least in part, this preference seems to be due to the T cells located in PP, which have been shown to stimulate switching to IgA production by cognate interactions and production of TGF-beta. Postswitch B cells expressing surface IgA respond to IL-5, a cytokine produced by T cells in GALT. Terminal differentiation to IgA-producing plasma cells in the lamina propria may be driven by IL-6, which can be produced by a variety of cells in the lamina propria and by epithelial cells. T cells in the lamina propria have an assortment of surface markers consistent with both activation and memory and appear to produce a variety of cytokines in the local environment that presumably act in normal host defense. IEL consist mainly of CD8+ T cells. They have been shown to produce IFN-gamma and, very likely, other cytokines that presumably act in a paracrine fashion on local enterocytes. How these cells and cytokines are perturbed during intestinal inflammation is currently being defined. A certain assortment of cytokines are greatly increased in IBD. This assortment, including IL-1, IL-6, and IL-8, is elevated in a wide variety of chronic inflammatory states in other tissues as well. A critical requirement for cytokines to exert their effects is the expression of specific receptors on target cells. Virtually nothing is known about this aspect of mucosal immunity, but receptor expression on mucosal cells must be defined before we will be able to understand the complex interactions among lymphoid cells, the cytokines they produce, and the local stromal and epithelial cells.
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PMID:Cells and cytokines in mucosal immunity and inflammation. 151 47

Epithelia from several sites exhibit inducible secretion of interleukin 8 (IL-8). This study aimed to characterise secretion of IL-8 by colonic epithelial cells in vitro. Colonic crypt cells were isolated enzymatically from resected colon and the IL-8 content of culture supernates was measured by ELISA. The rate of secretion of IL-8 accelerated and levels of IL-8 transcripts increased appreciably during culture. Exposure to tumour necrosis factor alpha (TNF alpha) failed to increase secretion further. Secretion was not induced by the enzymatic digestion or by serum used in the culture medium but was significantly inhibited by butyrate, by a mean of 23%. Control experiments indicated that colonic crypt cells were the likely source. The secretion of IL-8 over 24 hours by cells from uninflamed mucosa of patients with ulcerative colitis or Crohn's disease was more than twofold that from normal cells, while that from cancer bearing colons was normal. TNF alpha (10 mM) significantly suppressed IL-8 secretion only in the ulcerative colitis group and the change was different to those in the normal (p = 0.007) and Crohn's disease groups (p = 0.012). Cells from inflamed areas secreted more IL-8 than those from autologous uninflamed areas (p = 0.009) but responses to modulating factors were no different. The induction of IL-8 secretion by colonic crypt cells in vitro is probably a response to injury associated with isolation and culture. It is suppressed by butyrate and increased in inflammatory bowel disease independently of the presence of mucosal inflammation. Whether epithelial derived IL-8 plays a part in the pathogenesis of inflammatory bowel disease is not yet clear.
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PMID:Interleukin 8 secretion by colonic crypt cells in vitro: response to injury suppressed by butyrate and enhanced in inflammatory bowel disease. 748 42

Tissue and plasma concentrations of several cytokines are increased in patients with inflammatory bowel disease (IBD). Platelets play an important role in inflammation and circulate in an activated state in patients with IBD. This study assesses the expression of IL-8 and IL-1 receptors on the surface of platelets from patients with IBD using phycoerythrin (PE)-labelled recombinant human rhIL-1 beta and rhIL-8 and flow cytometry. The percentage IL-1R expressing platelets (median and interquartile range IQR) in the IBD group was 8.7% (5.5-18.2) compared to 4.2% (2.3-6.1) in controls (P = 0.02). The percentage IL-8R expressing platelets in the IBD group was 22.5% (16.5-27.9) and 9.2% (4.3-9.6) in controls (P < 0.001). Furthermore, platelet IL-1R expression in patients with IBD was inversely related to the total daily dose of steroids (r = 0.71, P < 0.01 linear regression analysis). Finally, platelet rich plasma from healthy controls was stimulated with rhIL-1 beta and rhIL-8 and assessed for activation dependent expression of platelet aGPIIb/IIIa and CD62 (p-selectin, GMP-140). IL-1 beta and IL-8 in vitro significantly and specifically activated the platelets. The surface membrane of platelets is able to express functional IL-1R and IL-8R, the expression of which is significantly increased in IBD. Interleukin-1 beta and IL-8 modulate platelet activation in vitro indicating a target role for platelet function in inflammation.
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PMID:Platelets in ulcerative colitis and Crohn's disease express functional interleukin-1 and interleukin-8 receptors. 753 43

Cytokines are important immunoregulatory mediators. Their contribution to the pathogenesis of acute and chronic gastroenterological disorders is obvious. Increased expression of interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor (TNF) can be detected in inflammatory bowel disease. During the last few years it has also been recognized that activated leukocytes have an important role in the multisystem involvement of acute pancreatitis. Activation of leukocytes is an early event during severe acute pancreatitis, and it may be a pathogenetic factor in the severity of the disease. The review summarizes the recent findings in the field of inflammatory cytokines with particular attention of TNF, IL-1, IL-6, and IL-8 during severe acute pancreatitis and underscores the role of the activated leukocytes in the pathogenesis of complicated acute pancreatitis.
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PMID:[Inflammatory mediators in acute pancreatitis (theoretical considerations)]. 765 17

Inflammatory bowel disease (IBD) is characterized by T-cell activation and mucosal influx of inflammatory cells partly mediated by increased local release of cytokines and chemokines. Increased levels of activated platelets are reported in IBD. Activated platelets induce endothelial cells in vitro to secrete several cytokines and growth factors and to express adhesion molecules. This study investigates the expression of interleukin-1 (IL-1), IL-8 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors on circulating platelets from patients with IBD and healthy controls and assesses the in vitro effect of various concentrations of IL-1 beta, IL-8 and GM-CSF on platelet activation in healthy controls. Flow cytometry was performed to quantify the percentage of platelets binding phycoerythrin (PE) labeled recombinant human IL-1 beta, IL-8 and GM-CSF. Platelet activation was assessed using fluorochrome labeled anti-GMP-140, an activation-dependent antigen. Results are expressed as percentage cytokine receptor expressing platelets (median and interquartile range IQR). Platelets from patients with IBD expressed significantly more cytokine receptors compared to healthy controls: IL-1R [8.7% (5.5-18.2) vs 3.1% (2.4-4.8), p < 0.05], IL-8R [22.5% (18.1-27.9) vs 8% (4.5-9.2), p < 0.001)], GM-CSFR [25.9% (16.1-39.2) vs 3.9% (2.7-3.9), p < 0.001]. The percentage of activated platelets was significantly increased after in vitro stimulation with IL-1 beta, IL-8 and GM-CSF. We conclude that cytokines and chemokines modulate platelet activation through specific, functional receptors which are upregulated in IBD.
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PMID:[Thrombocytes express functional cytokine receptors in patients with Crohn disease and ulcerative colitis]. 776 8

Altered peripheral neutrophil function is a feature of IBD that may contribute to the chronicity and extragastrointestinal manifestations of this disease, but clinical evidence for such alterations is confounded by variations in patient characteristics, disease onset, and use of therapeutics that can influence neutrophil function. The use of a rat model of colitis has permitted us to characterize, in a controlled manner, the causal relationship between colitis and altered peripheral neutrophil function. At various times after induction of colitis with trinitrobenzene sulfonic acid (TNBS), peripheral neutrophils were isolated and assays of phagocytosis, chemotaxis, leukotriene B4 (LTB4) synthesis, and superoxide production were performed using a variety of stimuli. Circulating neutrophil numbers increased about fourfold within 12 hr of TNBS administration and returned to normal levels over the following two weeks. LTB4 synthesis in response to calcium ionophore decreased at 12 hr after induction of colitis, then returned to control levels. The chemotactic responses of peripheral neutrophils to LTB4 and FMLP in vitro and to LTB4 and IL-8 in vivo were profoundly suppressed through the two-week study period. Phagocytosis of nitroblue tetrazolium was significantly enhanced (ca. threefold) at 12 hr after induction of colitis and remained elevated throughout the study period. Superoxide production was also significantly elevated in the early phase of colitis (by ca. fourfold), but was not different from control levels at seven and 14 days. These results demonstrate that colonic inflammation profoundly influences peripheral blood neutrophil function, although the direction and magnitude of the alteration varied among the various functions assessed. The prolonged depression of chemotactic activity may represent a physiological reaction to limit the inflammatory response.
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PMID:Alterations in rat peripheral blood neutrophil function as a consequence of colitis. 782 Nov 10

IL-8 is generating increasing interest as a powerful neutrophil chemoattractant and activator. To elucidate the mechanisms of neutrophil infiltration in inflammatory bowel disease, we examined 33 patients with ulcerative colitis (UC), 18 with Crohn's disease (CD), eight with some other type of colitis, and 18 normal control subjects for measurement of IL-8 in homogenates of colonic biopsy specimens. The affected colonic mucosa was found to contain significantly more IL-8 in patients with active inflammatory bowel disease than in patients with inactive disease (UC, P < 0.001; CD, P < 0.001), in patients with other types of colitis (UC, P < 0.05; CD, P < 0.01), or in normal control subjects (UC, P < 0.001; CD, P < 0.001). Colonic IL-8 levels correlated significantly with the macroscopic grade of local inflammation, especially in patients with UC (P < 0.001). Colonic IL-8 levels also correlated well with the neutrophil numbers in mucosal tissue (UC, r = 0.950, P < 0.001; CD, r = 0.940, P < 0.001), and with colonic IL-1 beta (r = 0.911, P < 0.001) and tumour necrosis factor-alpha (TNF-alpha) levels (r = 0.604, P < 0.001) in patients with these two conditions. These data suggest a potential role for IL-8 and its regulatory cytokines IL-1 and TNF-alpha in mediating neutrophil infiltration of the gut wall in inflammatory bowel disease.
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PMID:IL-8 as an important chemoattractant for neutrophils in ulcerative colitis and Crohn's disease. 800 12

Interleukin-8 (IL-8) is a potent cytokine for recruitment and activation of neutrophils. To visualize its distribution in the intestinal mucosa and to understand better its possible role in the induction and promotion of inflammatory bowel disease, expression of the IL-8 gene was analyzed in resected bowel segments of 14 patients with active Crohn's disease or ulcerative colitis. In situ hybridization with IL-8 anti-sense RNA probes revealed strong and specific signals in the histologically affected mucosa. The number of cells expressing IL-8 gene correlated with the histological grade of active inflammation. In accordance with the characteristic histological signs of active disease, IL-8-expressing cells were diffusely distributed over the entire affected mucosa in patients with ulcerative colitis, whereas in patients with Crohn's disease, IL-8-expressing cells showed a focal distribution pattern. Cells expressing IL-8 were mainly located at the base of ulcers, in inflammatory exudates on mucosal surfaces, in crypt abscesses, and at the border of fistulae. Analysis of semi-serial sections pointed to macrophages, neutrophils, and epithelial cells as possible sources of this cytokine in active inflammatory bowel disease. We consistently failed to detect IL-8 messenger RNA in the mucosa of uninvolved bowel segments and in normal-appearing control mucosa of patients with colon cancer. In contrast, tissue specimens from two patients with acute appendicitis displayed IL-8-expressing cells in the mucosa. These results support the notion that IL-8 plays and important but nonspecific role in the pathogenesis of inflammatory bowel disease and that the production of IL-8 messenger RNA is restricted to areas with histological signs of inflammatory activity and mucosal destruction.
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PMID:Expression of interleukin-8 gene in inflammatory bowel disease is related to the histological grade of active inflammation. 817 48

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