interleukin-8 and Esophagitis

Gastroesophageal reflux disease (GERD) is one of the most common problems in clinical practice today. It is widely believed that functional and structural abnormalities of the gastroesophageal junction as well as an abnormal exposure to gastroduodenal contents are the main contributors to its pathogenesis. Novel findings of the inflammatory process in GERD suggest a far more complex process involving multifaceted inflammatory mechanisms. This review summarizes knowledge about the expression of inflammatory mediators in GERD and their potential cellular sources and provides an integrated concept of disease pathogenesis. In addition we evaluate the contribution of inflammatory mediators to well-known complications of GERD, namely motility abnormalities, fibrosis, and carcinogenesis. Novel findings regarding the pathophysiology of esophageal inflammation should enhance our understanding of GERD and its complications and provide new treatment insights.

Topics: Animals; Endothelial Cells; Esophageal Motility Disorders; Esophageal Neoplasms; Esophagitis; Esophagogastric Junction; Fibrosis; Gastroesophageal Reflux; Gastrointestinal Motility; Humans; Inflammation Mediators; Interleukin-1; Interleukin-6; Interleukin-8; Mesoderm; Platelet Activating Factor; Reactive Oxygen Species

To study whether cytokine markers may improve predictive accuracy of radiation esophagitis (RE) in non-small cell lung cancer (NSCLC) patients.. A total of 129 patients with stage I-III NSCLC treated with radiotherapy (RT) from prospective studies were included. Thirty inflammatory cytokines were measured in platelet-poor plasma samples. Logistic regression was performed to evaluate the risk factors of RE. Stepwise Akaike information criterion (AIC) and likelihood ratio test were used to assess model predictions.. Forty-nine of 129 patients (38.0%) developed grade ≥2 RE. Univariate analysis showed that age, stage, concurrent chemotherapy, and eight dosimetric parameters were significantly associated with grade ≥2 RE (p < 0.05). IL-4, IL-5, IL-8, IL-13, IL-15, IL-1α, TGFα and eotaxin were also associated with grade ≥2 RE (p < 0.1). Age, esophagus generalized equivalent uniform dose (EUD), and baseline IL-8 were independently associated grade ≥2 RE. The combination of these three factors had significantly higher predictive power than any single factor alone. Addition of IL-8 to toxicity model significantly improves RE predictive accuracy (p = 0.019).. Combining baseline level of IL-8, age and esophagus EUD may predict RE more accurately. Refinement of this model with larger sample sizes and validation from multicenter database are warranted.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Non-Small-Cell Lung; Cytokines; Esophagitis; Female; Humans; Interleukin-8; Logistic Models; Lung Neoplasms; Male; Middle Aged; Models, Statistical; Neoplasm Grading; Predictive Value of Tests; Prospective Studies; Radiation Injuries; Radiotherapy Dosage; Risk Factors

Esophageal epithelial cells are an initiating cell type in esophageal inflammation, playing an essential role in the pathogenesis of gastroesophageal reflux disease (GERD). A new tissue-derived cytokine, interleukin-33 (IL-33), has been shown to be upregulated in esophageal epithelial cell nuclei in GERD, taking part in mucosal inflammation. Here, inflammatory cytokines secreted by esophageal epithelial cells, and their regulation by IL-33, were investigated.. In an in vitro stratified squamous epithelial model, IL-33 expression was examined using quantitative RT-PCR, western blot, ELISA, and immunofluorescence. Epithelial cell secreted inflammatory cytokines were examined using multiplex flow immunoassay. IL-33 was knocked down with small interfering RNA (siRNA) in normal human esophageal epithelial cells (HEECs). Pharmacological inhibitors and signal transducers and activators of transcription 1 (STAT1) siRNA were used to explore the signaling pathways.. Interferon (IFN)γ treatment upregulated nuclear IL-33 in HEECs. Furthermore, HEECs can produce various inflammatory cytokines, such as IL-6, IL-8, monocyte chemoattractant protein 1 (MCP-1), regulated on activation normal T-cell expressed and presumably secreted (RANTES), and granulocyte-macrophage colony-stimulating factor (GM-CSF) in response to IFNγ. Nuclear, but not exogenous IL-33, amplified IFN induction of these cytokines. P38 mitogen-activated protein kinase (MAPK) and janus protein tyrosine kinases (JAK)/STAT1 were the common signaling pathways of IFNγ-mediated induction of IL-33 and other cytokines.. Esophageal epithelial cells can actively participate in GERD pathogenesis through the production of various cytokines, and epithelial-derived IL-33 might play a central role in the production of these cytokines.

Topics: Blotting, Western; Cell Nucleus; Cells, Cultured; Cytokines; Epithelium; Esophagitis; Esophagus; Fluorescent Antibody Technique; Gastroesophageal Reflux; Humans; Interferon-gamma; Interleukin-33; Interleukin-6; Interleukin-8; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Tumor Necrosis Factor-alpha

The purpose of this study was to assess the the efficacy of oral glutamine (GLN) in prevention of acute radiation-induced esophagitis in patients with lung cancer and determine the predictive role of clinical and dosimetric parameters.. Thirty-two patients diagnosed with lung cancer were studied prospectively. Sixteen patients (50%) received prophylactic powdered GLN orally in doses of 10g/8h. Patients were treated 2 Gy per fraction daily, 5 days a week. We evaluated the grading of esophagitis daily at the end of each fraction of each treatment day until a cumulative dose of 50 Gy was reached. The primary end point was radiation-induced esophagitis.. All patients tolerated GLN well. Toxicity grade, weight loss, serum cytokine levels and esophageal transit times exhibited statistically significant improvement in the GLN receiving group. GLN suppressed the inflammation related to the disease and treatment and reduced toxicity with statistical significance.. This study suggests a benefical role of oral GLN use in prevention and/or delay of radiation-induced esophagitis, in terms of esophageal transit time and serum immunological parameters, as well as weight loss.

Topics: Dietary Supplements; Esophagitis; Glutamine; Humans; Interleukin-1beta; Interleukin-6; Interleukin-8; Lung Neoplasms; Prospective Studies; Quality of Life; Radiation Injuries; Radiotherapy Dosage; Tumor Necrosis Factor-alpha

Helicobacter pylori (H. pylori) infection generally protects patients from erosive esophagitis through reduction of acid production due to gastric mucosal atrophy. However, there are H. pylori infected patients who still have erosive esophagitis. The reason for this discrepancy remains unclear. We have previously reported that polymorphisms in IL-8 promoter region influence the susceptibility of H. pylori related diseases. On the other hand, nucleotide-binding oligomerization domain 1 (NOD1) is known to play an important role in H. pylori infection. Hence, we hypothesized polymorphisms of these two molecules in H. pylori infected patients may influence the susceptibility to erosive esophagitis. Genomic DNA was extracted from 312 H. pylori infected Japanese, consisting of 110 patients with erosive esophagitis and 202 healthy controls. ND1+32656 T/GG and IL-8-251 A/T polymorphisms were genotyped by direct sequencing. ND1+32656 GG allele and IL-8-251 T/T allele increased the risk of erosive esophagitis with odds ratio (OR) of 1.9 (95% confidence interval (CI) 1.1-3.0, p=0.013) and 1.7 (95% CI 1.1-2.8, p=0.036), respectively. Combination of these two alleles increased the risk with OR of 3.2(95% CI 1.6-6.5, p=0.001). In conclusion, ND1+32656 GG and IL-8-251 T/T allele may be associated with less reactivity to H. pylori infection, and may increase the risk of erosive esophagitis even in H. pylori infected Japanese population.

Topics: Aged; Alleles; Asian People; Atrophy; Case-Control Studies; Esophagitis; Female; Gastric Acid; Gastric Mucosa; Gene Frequency; Genetic Predisposition to Disease; Genotype; Helicobacter Infections; Helicobacter pylori; Humans; Interleukin-8; Japan; Male; Middle Aged; Nod1 Signaling Adaptor Protein; Polymorphism, Single Nucleotide

The incidence of esophageal adenocarcinoma has increased significantly in the western world over the last 20 yr. Most cases arise in a background of chronic gastroesophageal reflux, and specialized intestinal metaplasia in Barrett's esophagus is frequently an antecedent phenotype or evident in association with adenocarcinoma. The molecular events that characterize the pathway from inflammation to metaplasia to dysplasia and adenocarcinoma are poorly understood.. To examine the expression of the proinflammatory cytokines IL-8 and IL-1beta along the esophagitis, metaplasia, dysplasia, and adenocarcinoma pathway, and to correlate this with histological changes and expression of the transcription factor NF-kappaB.. Fresh biopsy specimens were collected from patients with reflux esophagitis (n=15), Barrett's esophagus (n=35), Barrett's adjacent to adenocarcinoma (n=8), and esophageal adenocarcinoma (n=35). IL-8 and IL-1beta expression were measured using enzyme-linked immunosorbent assay. NF-kappaB expression was measured by electrophoretic mobility shift assay.. Elevated expression of NF-kappaB was found in 2 (13%) out of 15 patients with reflux esophagitis, 21 (60%) out of 35 patients with Barrett's esophagus, and 28 (80%) out of 35 patients with esophageal adenocarcinoma. All 5 patients with Barrett's esophagus and high-grade dysplasia showed elevated expression of NF-kappaB. IL-8 and IL-1beta were significantly increased in esophagitis, Barrett's, and adenocarcinoma compared with squamous epithelium, and in adenocarcinoma compared with all other groups. There was a stepwise increase in the expression of IL-8, IL-1beta, and NF-kappaB from normal through Barrett's epithelium to adenocarcinoma in eight cases of esophageal adenocarcinoma. The levels of both IL-8 and IL-1beta in adenocarcinoma patients correlated with stage of disease. Patients with adenocarcinoma who were NF-kappaB positive had significantly higher levels of both IL-8 (p=0.04) and IL-1beta (p=0.03) compared to adenocarcinoma patients who were NF-kappaB negative.. The proinflammatory cytokines IL-8 and IL-1beta are elevated in esophagitis and Barrett's epithelium, and markedly elevated in adenocarcinoma. NF-kappaB activation is infrequent in esophagitis, but is increased in Barrett's epithelium and adenocarcinoma. The association of NF-kappaB activation with cytokine upregulation was only evident in patients with adenocarcinoma. These patterns may play an important role in Barrett's inflammation and tumourigenesis, and inhibition of the NF-kappaB/proinflammatory cytokine pathway may be an important target for future chemoprevention strategies.

Topics: Adenocarcinoma; Barrett Esophagus; Biomarkers; Biopsy; Electrophoresis; Endoscopy, Digestive System; Enzyme-Linked Immunosorbent Assay; Esophageal Neoplasms; Esophagitis; Female; Gastroesophageal Reflux; Humans; Interleukin-1; Interleukin-8; Intestinal Mucosa; Male; Metaplasia; Middle Aged; NF-kappa B; Precancerous Conditions; Prospective Studies