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

Interleukin-8 (IL-8) and nitric oxide (NO) may be important mediators in the pathogenesis of chronic idiopathic inflammatory bowel disease (CIIBD), but their roles in disease activity in ulcerative colitis (UC) and Crohn's disease (CD) are uncertain. The aim of this study was to measure mRNA for IL-8 and inducible NO synthase (iNOS) in small mucosal biopsies from untreated patients at first presentation and to relate these measurements to the histological levels of polymorph infiltration graded on a ten-point scale. For this purpose, a sensitive enzyme-linked oligonucleotide chemiluminescent assay (ELOCA) was developed to quantitate reverse transcription-polymerase chain reaction (RT-PCR) products amplified from RNA from paired biopsy samples. The levels of IL-8 and iNOS mRNAs were calculated as ratios of the RT-PCR products to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) RT-PCR product. In UC patients, median values of IL-8/GAPDH and iNOS/GAPDH were significantly elevated compared with controls and CD. However, in both UC and CD, the IL-8/GAPDH and iNOS/GAPDH ratios correlated significantly with polymorph infiltration. ELOCA enabled quantitation of multiple mRNAs in small mucosal biopsies from untreated patients with CIIBD and supported a role for IL-8 and iNOS in acute inflammation in both UC and CD.
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PMID:Interleukin-8 and inducible nitric oxide synthase mRNA levels in inflammatory bowel disease at first presentation. 907 8

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

The intestinal epithelial cell population is comprised of a dynamic continuum, ranging from undifferentiated, actively proliferating crypt cells, to mature absorptive villus enterocytes, lacking mitotic capacity. Under normal conditions, the constant loss of differentiated villus tip cells via apoptosis leads to a complete renewal of the epithelial cell population every few days. The physiological factors regulating enterocyte proliferation, maturation and apoptosis in health, as well as those that modulate these events in disease states remain largely unknown. It has been demonstrated in vitro that immature crypt cell proliferation is stimulated by factors such as TGF alpha and TNF alpha, whereas TFG beta and IFN gamma inhibit mitotic activity. Further studies showed that intestinal epithelial cells are able to produce and secrete several cytokines such as IL6, IL8, TNF alpha, TGF alpha and TGF beta, indicating the potential for autocrine and paracrine responses. A variety of immune mediated bowel disorders, including celiac disease, Crohn's disease and ulcerative colitis, are characterized by accelerated epithelial cell turnover and apoptosis, leading to altered crypt/villus morphology. There is increasing evidence that these changes, and the accompanying functional alterations of the bowel epithelium, are mediated by the cytokines released from infiltrating inflammatory cells, as well as from enterocytes themselves in an autocrine fashion.
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PMID:Cytokine--intestinal epithelial cell interactions: implications for immune mediated bowel disorders. 955 84

Inflammatory bowel disease (IBD) denotes chronic inflammatory disorders of gastrointestinal tract of unknown etiology that comprises 2 major groups: ulcerative colitis (UC) and Crohn's disease (CD). Disregulation of the intestinal immune system both at humoral and cellular level constitutes an important element in the multifactorial pathogenesis of IBD. The expression of pro-inflammatory cytokines, most notably IL-1, IL-6, TNF-alpha and chemokines (IL-8, ENA-78, MCP-1, RANTES) in intestinal mucosa from IBD patients is markedly enhanced, however, it is not always accompanied by increases in cytokines' serum levels. In IBD also significant changes occur in the tissue expression of immunoregulatory cytokines: increased levels of IL-2 mRNA and IFN-gamma mRNA, and decreased expression of IL-4 were found in affected intestinal mucosa. Chronic intestinal lesions of patients with Crohn's disease are associated with a Th1 type cytokine profile. The clinical effectiveness of anti-TNF-alpha antibodies and of IL-10 has been demonstrated in steroid-refractory Crohn's disease patients. The data demonstrating the role of cytokines in the pathogenesis of IBD should be carefully analyzed because of limitations imposed by the patient- and sample-related parameters. Further investigations will clarify the significance of the impairments in cytokine network for the initiation and progression of the IBD.
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PMID:Cytokines in inflammatory bowel disease. 970 46

To elucidate the possible role of proinflammatory cytokines in inflammatory bowel disease, the expression and localization of interleukin (IL) -6 and IL-8 mRNAs were examined in colonic biopsy specimens obtained from 10 patients with active ulcerative colitis (UC), 5 with inactive UC, 6 with Crohn's disease (CD), and 5 normal controls. In situ hybridization with digoxigenin-labeled probes and immunohistochemistry for both cytokines were performed. The IL-6 mRNA expression was enhanced in the inflamed mucosa in 4 of 6 CD patients, while that of UC patients stayed at baseline. In contrast, IL-8 mRNA expression was apparently augmented (P = 0.044) in 7 of 10 active UC and 3 of 6 CD patients (NS). The cell count positive for IL-8 mRNA per unit area was definitely increased in moderate/severe UC when compared to mild UC (53.1 +/- 14.4/mm2 vs 9.0 +/- 5.1/mm2, P = 0.028) according to the degree of inflammation. IL-6 mRNA positive cells in CD were preferentially located in deeper lamina propria than IL-8 mRNA positive cells in UC. Interestingly, IL-8 mRNA was expressed in the mucosal epithelial cells in one UC patient. The patients treated by corticosteroids tended to show suppressed expression of each mRNA, except one patient with intractable UC. Our data suggest enhanced expression of mucosal IL-6 mRNA in CD and of IL-8 mRNA in UC by infiltrating mononuclear cells, indicating the distinct participation of each cytokine in the pathogenesis of UC and CD. Moreover, intestinal epithelial cells in UC occasionally exhibit IL-8 mRNA.
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PMID:Mucosal expression of interleukin-6 and interleukin-8 messenger RNA in ulcerative colitis and in Crohn's disease. 975 75

Crohn's disease (CD) lesions are characterized by a marked neutrophilic infiltrate associated with enhanced mucosal IL-8, contrasting with low serum IL-8 levels. The aim of this study was to investigate the effects of circulating GROalpha and IL-8 on neutrophil priming and migration. The expression of surface molecules involved in rolling (CD62L, CD15) and firm adhesion (Mac-1 and LFA-1) to endothelial cells was assessed by flow cytometry, while the chemotactic response of PMN to IL-8 and to fMLP was investigated in a Boyden chamber assay. In addition, IL-8 and GROalpha levels were determined by ELISA in plasma samples and in culture supernatants of purified polymorphonuclear neutrophils (PMN) and peripheral blood mononuclear cells (PBMC) from patients with CD and healthy blood donors. This study revealed an upregulation of CD11b (Mac-1) membrane expression on circulating PMN from patients with CD, as assessed by the mean fluorescence intensity which reflects antigen density. Furthermore, an enhanced chemotactic response towards both fMLP and IL-8 of PMN from CD patients was observed. Despite often undetectable levels of circulating IL-8, all plasma samples were positive for GROalpha, with a significant increase in CD patients when compared to donors. In vitro, equivalent concentrations of GROalpha were able to increase the IL-8 driven chemotaxis of PMN. In conclusion, blood PMN from patients with CD showed an enhanced capacity to be recruited into inflammed intestinal mucosa, which could be due to an increased expression of CD11b (Mac-1) as well as an increased chemotactic response toward fMLP or IL-8. This priming effect of PMN in CD may partly occur through elevated circulating GROalpha levels.
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PMID:Circulating growth-regulator oncogene alpha contributes to neutrophil priming and interleukin-8-directed mucosal recruitment into chronic lesions of patients with Crohn's disease. 988 9

Anecdotal reports suggest that smoking may be beneficial for patients with inflammatory bowel disease (IBD) as nicotine may act through inflammatory mediators within the colonic mucosa. Furthermore, there is increasing evidence that cytokines play a pathologic role in IBD. Our aim was to determine the effects of cigarette smoking on cytokine levels in the colonic mucosa of patients with and without IBD. Mucosal biopsies were obtained from 10 patients with Crohn's disease (CD), 10 with ulcerative colitis (UC), and 10 healthy controls. Five of 10 patients in each of the three groups were smokers and five were nonsmokers. Concentrations of interleukin (IL)-1beta, IL-2, IL-6, and IL-8 were determined using enzyme-linked immunosorbent assay (ELISA). Cytokine levels of smokers were compared with nonsmokers in each group and with controls. Results were analyzed using the Mann-Whitney test; significance was set at p<0.05. The concentration of IL-8 was significantly higher in healthy controls who smoke compared with nonsmokers and significantly reduced in smokers with CD compared with nonsmokers with CD. Moreover, concentrations of IL-1beta and IL-8 were significantly reduced in smokers with UC compared with nonsmokers with UC. Smokers had significantly elevated levels of IL-8 in the colonic mucosa. Smokers with IBD had a significant reduction in cytokine levels; specifically, IL-1beta and IL-8 for patients with UC and IL-8 for patients with CD. Further studies are warranted to determine if this reduction in cytokine levels is histologically and clinically significant.
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PMID:The influence of cigarette smoking on cytokine levels in patients with inflammatory bowel disease. 1033 74

Ulcerative colitis and Crohn's disease are characterized by chronic intestinal inflammation. Intestinal bacteria initiate the activation of intestinal inflammatory processes, which are mediated by proinflammatory cytokines and chemokines. In inflammatory bowel disease, intestinal inflammation is not downregulated, in part due to defective or absent inhibitory processes. Studies to date have demonstrated that IL-8, MCP-1, and ENA-78 are highly expressed in the intestinal mucosa in areas of active Crohn's disease and ulcerative colitis. Neutrophils and macrophages in the inflamed intestine synthesize and secrete large amounts of chemokines in patients with inflammatory bowel disease. Increased chemokine expression has also been observed in epithelial cells, endothelial cells, and smooth muscle cells. Future trials of specific agents capable of inhibiting chemokine synthesis and secretion or blocking chemokine-chemokine receptor interaction will be important to study in patients with ulcerative colitis and Crohn's disease.
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PMID:Chemokines in the inflammatory bowel diseases. 1053 2

Assessment of disease activity in inflammatory bowel disease (IBD), i.e., ulcerative colitis (UC) and Crohn's disease (CD), is done using clinical parameters and various biological disease markers. Ideally, a disease marker must: be able to identify individuals at risk of a given disorder, be disease specific, mirror the disease activity and, finally, be easily applicable for routine clinical purposes. However, no such disease markers have yet been identified for IBD. In this article, classical disease markers including erythrocyte sedimentation rate, acute phase proteins (especially orosomucoid and CRP), leukocyte and platelet counts, albumin, neopterin, and beta2-microglobulin will be reviewed together with emerging disease markers such as antibodies of the ANCA/ASCA type, cytokines (e.g., IL-1, IL-2Ralpha, IL-6, IL-8, TNF-alpha, and TNF-alpha receptors) and with various adhesion molecules. It is concluded that none of the pertinent laboratory surrogate markers of disease activity in IBD are specific or sensitive enough to replace basic clinical observation such as the number of daily bowel movements, general well-being, and other parameters in parallel. Further studies are highly warranted to identify and assess the clinical importance and applicability of new laboratory markers for the diagnosis or the disease activity of IBD.
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PMID:Established and emerging biological activity markers of inflammatory bowel disease. 1092 11

Macrophages are important in the host's immunological and inflammatory responses. There is a large population of these cells in the normal intestinal mucosa where they represent the major antigen presenting cell population capable of determining the type of T cell responses that develop to luminal antigens. Studies suggest that the normal intestinal macrophages cannot be easily induced to mediate acute inflammatory responses. In active inflammatory bowel disease there is an increase in the mucosal macrophage population, derived from circulating monocytes. These recruited macrophages are phenotypically different from the resident population of cells and play a major role in mediating the chronic mucosal inflammation seen in patients with ulcerative colitis and Crohn's disease. They secrete many cytokines that are important in the proinflammatory responses, such as interleukin (IL)-1, IL-6, IL-8, IL-12, IL-18, and tumor necrosis factor-alpha. They also release reactive metabolites of oxygen and nitrogen and proteases that degrade the extracellular matrix. Macrophages also appear to be important during resolution of inflammation and repair of the intestinal mucosa that occurs during disease remission.
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PMID:The key role of macrophages in the immunopathogenesis of inflammatory bowel disease. 1070 Nov 46


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