interleukin-8 and Gastroenteritis

This study systematically evaluated the clinical efficacy and safety of Fengliao Changweikang prescription for treating acute gastroenteritis(AGE). The databases of CNKI, Wanfang, VIP, SinoMed, Medline, Cochrane Library and two clinical trial registration platforms were retrieved from inception to August 30, 2022, to collect randomized controlled trial(RCT) on Fengliao Changweikang prescription treating AGE. Two researchers independently conducted literature screening, data extraction, and risk of bias assessment according to pre-established inclusion and exclusion criteria. RevMan 5.4.1 was used for data analysis. Finally, 18 RCTs were included, involving 3 489 patients. Meta-analysis showed that compared with conventional western medicine, Fengliao Changweikang prescription improved the relief rate of abdominal pain(RR=1.27, 95%CI[1.17, 1.38],P<0.000 01); Fengliao Changweikang prescription + conventional western medicine increased the cure rate(RR=1.43, 95%CI[1.12, 1.82], P=0.004), shortened the duration of diarrhoea(RR=-1.65, 95%CI[-2.44,-0.86], P<0.000 1), abdominal pain(RR=-1.46, 95%CI[-2.00,-0.92], P<0.000 01), vomiting(RR=-2.16, 95%CI[-2.51,-1.81], P<0.000 01) and fever(RR=-2.61, 95%CI[-4.00,-1.23], P=0.000 2), down-regulated the level of interleukin-8(IL-8)(RR=-1.07, 95%CI[-1.26,-0.88], P<0.000 01), IL-6(RR=-8.24, 95%CI[-8.99,-7.49], P<0.000 01) and hypersensitive C-reactive protein(hs-CRP)(RR=-3.04, 95%CI[-3.40,-2.69], P<0.000 01) and recurrence of AGE(RR=0.20, 95%CI[0.05, 0.90], P<0.04). In conclusion, Fengliao Changweikang prescription was safe in clinical application. It was beneficial to alleviate the clinical symptoms of diarrhea, abdominal pain, vomiting, and fever, and down-regulate the levels of some serum inflammatory factors in AGE patients. However, considering that few high-quality studies have evaluated the efficacy and safety of Fengliao Changweikang prescription in treatment of AGE, further evidence is needed in the future.

Topics: C-Reactive Protein; Drugs, Chinese Herbal; Gastroenteritis; Gene Expression; Humans; Interleukin-8; Treatment Outcome

Genetic epidemiology is an important discipline that is helping to unravel the aetiology and pathogenesis of complex human diseases. In the context of gastrointestinal malignancy, the paradigm model of host genetic influence on disease outcome is H. pylori-associated gastric adenocarcinoma. This cancer represents a classic example of an inflammation-induced malignancy and highlights the importance of host genetics in disease development. This chapter gives an insight into how genetic epidemiology can play an important role in the development of gastric cancer. Increasing our understanding of host genetics in cancer development may allow particularly susceptible individuals to be targeted for screening or treatment to reduce risk of future malignant transformation.

Topics: Adenocarcinoma; Cyclooxygenase 2; Gastroenteritis; Gastrointestinal Neoplasms; Genes, MHC Class II; Helicobacter Infections; Helicobacter pylori; Humans; Interleukin-1beta; Interleukin-8; Stomach Neoplasms; Tumor Necrosis Factor-alpha

Recently, the role of serine proteinases in the pathogenesis of inflammation and autoimmune diseases via interaction with the proteinase-activated receptor (PAR) has attracted attention. Activation of PAR has a pro-inflammatory effect through the overproduction of inflammatory cytokines such as interleukin (IL)-6 and IL-8. PAR(2) activation in human esophageal epithelial cells by trypsin induces NFkappaB- and AP-1-dependent IL-8 production in association with activation of p38 MAPK and ERK1/2, suggesting that esophageal inflammation may be induced by PAR(2) activation via reflux of trypsin. It has been also proposed that Helicobacter pylori (H. pylori) induces PAR expression in the gastric epithelial cells and H. pylori-derived serine proteinase promotes IL-8 production via PAR in the epithelial cells. In addition, an increase of PAR-dependent IL-8 production has been observed in H. pylori-infected human gastric mucosa, suggesting an important role for PAR(2) in the modulation of gastric inflammation associated with H. pylori. Recent studies have strongly indicated that tryptase and PAR are implicated in the pathogenesis of inflammatory bowel disease and experimental colitis. We demonstrated that anti-tryptase therapy may become a new therapeutic strategy in human ulcerative colitis. Thus, the role of PAR in the gastrointestinal tract has been gradually clarified, but further investigations are needed because the receptor has a variety of functions.

Topics: Animals; Drug Delivery Systems; Gastroenteritis; Gene Expression Regulation; Helicobacter Infections; Helicobacter pylori; Humans; Interleukin-8; Protease Inhibitors; Receptor, PAR-2; Trypsin

The free radicals derived from oxygen have been implicated in damage caused to the gastroduodenal mucosa. The association between the mucosal production of reactive oxygen radicals in the gastric antrum and duodenum, Helicobacter pylori density and duodenal ulcer has been previously described. The role of interleukin IL-8 in the inflammatory process and its relationship with reactive oxygen radicals has also been investigated. These results indicate that oxygen radicals play an important role in the mechanism of ulcer aggravation induced by a variety of different factors.

Topics: Duodenal Ulcer; Duodenum; Free Radicals; Gastric Mucosa; Gastroenteritis; Helicobacter pylori; Humans; Interleukin-8; Reactive Oxygen Species; Stomach Ulcer

Noroviruses (NoV) are the most common cause of epidemic gastroenteritis world-wide. NoV infections are often asymptomatic, although individuals still shed large amounts of NoV in their stool. Understanding the differences between asymptomatic and symptomatic individuals would help in elucidating mechanisms of NoV pathogenesis. Our goal was to compare the serum cytokine responses and faecal viral RNA titres of asymptomatic and symptomatic NoV-infected individuals. We tested serum samples from infected subjects (n = 26; 19 symptomatic, seven asymptomatic) from two human challenge studies of GI.1 NoV for 16 cytokines. Samples from prechallenge and days 1-4 post-challenge were tested for these cytokines. Cytokine levels were compared to stool NoV RNA titres quantified previously by reverse transcription-polymerase chain reaction (RT-qPCR). While both symptomatic and asymptomatic groups had similar patterns of cytokine responses, the symptomatic group generally exhibited a greater elevation of T helper type 1 (Th1) and Th2 cytokines and IL-8 post-challenge compared to the asymptomatic group (all P < 0·01). Daily viral RNA titre was associated positively with daily IL-6 concentration and negatively with daily IL-12p40 concentration (all P < 0·05). Symptoms were not associated significantly with daily viral RNA titre, duration of viral shedding or cumulative shedding. Symptomatic individuals, compared to asymptomatic, have greater immune system activation, as measured by serum cytokines, but they do not have greater viral burden, as measured by titre and shedding, suggesting that symptoms may be immune-mediated in NoV infection.

Topics: Adolescent; Adult; Asymptomatic Diseases; Feces; Female; Gastroenteritis; Host-Pathogen Interactions; Humans; Immunity, Innate; Interleukin-12 Subunit p40; Interleukin-6; Interleukin-8; Male; Norovirus; RNA, Viral; Severity of Illness Index; Th1 Cells; Th1-Th2 Balance; Th2 Cells; Viral Load; Virus Shedding

Human milk oligosaccharides (hMOs) can attenuate inflammation by modulating intestinal epithelial cells, but the mechanisms of action are not well-understood. Here, the effects of hMOs on tumor necrosis factor-α (TNF-α) induced inflammatory events in gut epithelial cells are studied.. The modulatory effects of 2'-fucosyllactose, 3-fucosyllactose (3-FL), 6'-sialyllactose, lacto-N-tetraose, lacto-N-neotetraose (LNnT), lactodifucotetraose (LDFT), and lacto-N-triaose (LNT2) on immature (FHs 74 Int) and adult (T84) intestinal epithelial cells with or without TNF-α are determined. Interleukin-8 (IL-8) secretion in FHs 74 Int and T84 are quantified to determine hMO induced attenuation of inflammatory events by ELISA. 3-FL, LNnT, and LDFT significantly attenuate TNF-α induced inflammation in FHs 74 Int, while LNT2 induces IL-8 secretion in T84. In addition, microscale thermophoresis assays and ELISA are used to study the possible mechanisms of interaction between effective hMOs and tumor necrosis factor receptor 1 (TNFR1). 3-FL, LNnT, and LDFT exert TNFR1 ectodomain shedding while LNnT also shows binding affinity to TNFR1 with a Kd of 900 ± 660 nM.. The findings indicate that specific hMO types attenuate TNF-α induced inflammation in fetal gut epithelial cells through TNFR1 in a hMO structure-dependent fashion suggest possibilities to apply hMOs in management of TNF-α dependent diseases.

Topics: Cell Line; Cell Survival; Gastroenteritis; Humans; Hydrolysis; Interleukin-8; Intestinal Mucosa; Milk, Human; Oligosaccharides; Protein Domains; Receptors, Tumor Necrosis Factor, Type I; Structure-Activity Relationship; Tumor Necrosis Factor-alpha

Lactic acid bacteria (LAB) "fermentates" confer a beneficial effect on intestinal function. However, the ability of new fermentations to improve LAB broth activity in preventing pathogen-induced intestinal inflammation and barrier dysfunction has not yet been studied. The objective of this study was to determine if broths of LAB fermented with

Topics: Anti-Bacterial Agents; Barbarea; Brassicaceae; Caco-2 Cells; Cell Survival; Coculture Techniques; Drug Resistance, Bacterial; Electric Impedance; Escherichia coli Infections; Escherichia coli O157; Fermentation; Gastroenteritis; Humans; Interleukin-8; Intestinal Mucosa; Lactobacillus acidophilus; Phytotherapy; Plant Extracts; Probiotics; Seeds

Topics: Bacterial Proteins; Bacterial Toxins; Base Sequence; Campylobacter coli; Campylobacter Infections; Cell Death; Gastroenteritis; Gene Expression Regulation, Bacterial; Genes, Bacterial; Genome, Bacterial; HT29 Cells; Humans; Interleukin-8; Necrosis; Phylogeny; Sequence Analysis; Virulence; Whole Genome Sequencing

Noroviruses (NoV) are the most common cause of epidemic gastroenteritis worldwide. The acute immune response to NoV in humans is poorly understood, hindering research on prevention and treatment. To elucidate the acute immune response and test for cytokine predictors of susceptibility to infection, serum samples from two human NoV challenge studies were tested for 16 cytokines. Subjects who became infected (n = 26) were age-matched with subjects who remained uninfected following NoV challenge (n = 26). Samples were tested from prechallenge and days 1-4 post-challenge. Cytokine responses were compared between infected and uninfected groups. Overall, infected individuals exhibited an elevation in T helper type 1 (Th1) and Th2 cytokines, as well as chemokines interleukin (IL)-8 and monocyte chemoattractant protein (MCP-1), compared to uninfected individuals (all P < 0.05). Most cytokines peaked on day 2 post-challenge in infected subjects, and tumour necrosis factor (TNF)-α, IL-8, and IL-10 remained elevated to day 3. The only cytokine elevated significantly among infected subjects to day 4 post-challenge was IL-10 (P = 0.021). Prechallenge cytokine concentrations were not predictive of infection status post-challenge. There were no significant changes in serum cytokines among NoV-challenged subjects who remained uninfected. These results suggest that NoV infection elicits a Th1-type response, with some Th2 activation. Persistent elevation of IL-10 among infected subjects is consistent with activation of adaptive immune responses, such as B cell expansion, as well as down-regulation of Th1 cytokines. This study presents the first comprehensive description of the acute cytokine response to GI.1 NoV in humans.

Topics: Adult; Caliciviridae Infections; Chemokine CCL2; Cytokines; Feces; Female; Gastroenteritis; Host-Pathogen Interactions; Humans; Interleukin-10; Interleukin-8; Male; Norovirus; Reverse Transcriptase Polymerase Chain Reaction; RNA, Viral; Th1 Cells; Th2 Cells; Time Factors; Tumor Necrosis Factor-alpha; Young Adult

Campylobacter jejuni is the most prevalent cause of bacterial gastroenteritis worldwide. Polyphosphate kinases 1 and 2 (PPK1 and PPK2) regulate several cellular processes, including the biosynthesis of the bacterial cell wall. Despite their importance, whether PPK1 and PPK2 modulate the composition of C. jejuni outer membrane constituents (OMCs) and consequently impact its interaction with host cells remains unknown. Our comparative analysis between C. jejuni wild type, Δppk1, and Δppk2 strains showed qualitative and quantitative differences in the total OMC composition among these strains. Importantly, these OMC variations observed on the C. jejuni polyphosphate kinase mutants are directly related to their capacity to invade, survive, and alter the immune response of intestinal epithelial cells in vitro. Specifically, sub-fractionation of the C. jejuni OMC indicated that OMC proteins are uniquely associated with bacterial invasion, whereas C. jejuni OMC proteins, lipids, and lipoglycans are all associated with C. jejuni intracellular survival. This study provides new insights regarding the function of polyphosphate kinases and their role in C. jejuni infection.

Topics: Anti-Infective Agents; Campylobacter Infections; Campylobacter jejuni; Cell Line; Epithelial Cells; Gastroenteritis; Humans; In Vitro Techniques; Interleukin-8; Molecular Targeted Therapy; Phosphotransferases (Phosphate Group Acceptor)

Rotavirus and norovirus are the most common known causes of viral gastroenteritis in children. This study examined the association between serum interleukin 6 (IL-6) and interleukin 8 (IL-8) levels and disease severity in the acute phase of rotavirus and norovirus gastroenteritis in children, and it also explored the role of fecal cytokine levels in children with viral and bacterial gastroenteritis.. This prospective study enrolled patients aged 4 months to 14 years admitted with acute gastroenteritis in a tertiary care center. Peripheral blood samples were collected for IL-6 and IL-8 assays within the first 3 days of diarrhea. Stool samples were obtained from the patients in the first 24 hours after admission.. Serum IL-6 and IL-8 were measured in children with viral (n = 66) and bacterial (n = 23) infections, and in healthy controls (n = 10). In the acute phase of gastroenteritis, a moderately positive correlation was found between serum IL-6 levels and disease severity (rs = 0.41, p < 0.01). Serum IL-8 levels correlated with the duration of fever (rs = 0.28, p = 0.03). Fecal IL-6 levels correlated with the maximum number of daily bowel movements (rs = 0.35, p < 0.05). Rotavirus infection induced significantly higher serum IL-8 levels than norovirus infection (p < 0.05). Receiver operating characteristic (ROC) curve analysis showed that absolute neutrophil count (ANC), maximum body temperature (BT), and Vesikari score were significant predictors in discriminating rotavirus from norovirus gastroenteritis.. IL-6 and IL-8 are involved in the pathogenesis of acute gastroenteritis in both rotavirus and norovirus. An ANC of less than 9000/mm(3), maximum BT of less than 38.2°C, and Vesikari score of less than 14 at the end of the course are potential predictors of norovirus infection in children compared with rotavirus gastroenteritis.

Topics: Acute Disease; C-Reactive Protein; Caliciviridae Infections; Child, Hospitalized; Child, Preschool; Feces; Female; Gastroenteritis; Humans; Infant; Interleukin-6; Interleukin-8; Male; Norovirus; Prospective Studies; Rotavirus Infections

There is evidence for low-grade inflammation in the pathophysiology of post-infectious irritable bowel syndrome (IBS). We assessed the degree of subclinical intestinal mucosal inflammation in diarrhea-predominant IBS (IBS-D) in a tropical setting.. In a prospective study over 1 year, we investigated 49 patients with IBS-D (cases; median age 34 years (range 18-59); M:F 36:13), diagnosed on Rome III criteria. 14 individuals with a family history of colon cancer (median age 46.5 years (range 23-56); M:F 6:8) were selected as controls. Stools of cases and controls were tested for calprotectin. During colonoileoscopy, serial biopsies were obtained. Mucosal mast cells, neutrophils, eosinophils and lymphocytes/plasma cell infiltrate were quantified. Tissue expression of IL-8 and IL-10 was assessed in biopsies by semi-quantitative RT-PCR.. A history suggestive of an episode of infectious diarrhea (ID) was present in 16/49 cases and 0/14 controls (p = 0.013). In cases, there were significantly more mucosal mast cells in the ileum and all segments of colon and significantly more eosinophils in the cecum. Tissue expression of IL-8 was significantly higher and IL-10 significantly lower in cases compared with controls (target/standard cDNA ratio, median (range) IL-8: 1.25 (0.75-2) vs. 0.85 (0.63-1.3), p < 0.0001, Mann-Whitney U test; IL-10: 0.33 (0-0.63) vs. 0.55 (0.5-0.7), p < 0.0001). There was a significant inverse correlation between IL-8 and IL-10 expression (Pearson correlation, (-) 0.509; p < 0.01).. There was evidence of subclinical intestinal mucosal inflammation in patients with IBS-D. The finding of increased eosinophils is novel, and may be of special relevance to IBS-D in the tropics.

Topics: Adolescent; Adult; Biomarkers; Biopsy; Case-Control Studies; Colon; Colonoscopy; Diarrhea; Eosinophils; Female; Gastroenteritis; Humans; Ileum; Interleukin-10; Interleukin-8; Intestinal Mucosa; Irritable Bowel Syndrome; Male; Middle Aged; Prospective Studies; Reverse Transcriptase Polymerase Chain Reaction; Sri Lanka; Tropical Climate; Young Adult

The lack of a standardized laboratory animal model that mimics key aspects of human shigellosis remains a major obstacle to addressing questions about pathogenesis, screening therapeutics, and evaluation of vaccines.. We characterized a piglet model for Shigella dysenteriae type 1.. Piglets developed acute diarrhea, anorexia, and dehydration, which could often be fatal, with symptom severity depending on age and dose. Bacteria were apparent in the lumen and on the surface epithelium throughout the gut initially, but severe mucosal damage and bacterial cellular invasion were most profound in the colon. Detached necrotic colonocytes were present in the lumen, with inflammatory cells outpouring from damaged mucosa. High levels of interleukin (IL)-8 and IL-12 were followed by high levels of other proinflammatory cytokines. Elevated levels of tumor necrosis factor-alpha, IL-1beta, IL-6, and IL-10 were detected in feces and in gut segments from infected animals. Bacteria were present inside epithelial cells and within colonic lamina propria. In contrast, an isogenic strain lacking Shiga toxin induced similar but milder symptoms, with moderate mucosal damage and lower cytokine levels.. We conclude that piglets are highly susceptible to shigellosis, providing a useful tool with which to compare vaccine candidates for immunogenicity, reactogenicity, and response to challenge; investigate the role of virulence factors; and test the efficacy of microbial agents.

Topics: Animals; Case-Control Studies; Colony Count, Microbial; Cytokines; Disease Models, Animal; Dysentery, Bacillary; Euthanasia, Animal; Feces; Gastroenteritis; Gastrointestinal Tract; Interleukin-12; Interleukin-8; Microscopy, Electron; Shigella dysenteriae; Swine

The mechanisms that lead to the development of skin lesions in patients with dermatitis herpetiformis (DH) are not known. We hypothesized that an ongoing immune response in the gut of patients with DH would result in an increase in circulating cytokines and be associated with endothelial cell activation, creating a proinflammatory environment in the skin. Skin biopsies from the normal-appearing inner arm of 11 DH patients, with no active skin lesions, and 12 normal subjects were analyzed for E-selectin (E-sel) and ICAM-1 mRNA. DH patients' skin expressed markedly increased levels of E-sel mRNA. Mean E-sel mRNA expression in DH skin was 1,271 (range 63.78-5861) times greater than that of a control, normal skin (P<0.001) with no significant increased expression of ICAM-1 mRNA. Serum levels of soluble E-selectin (sE-sel), IgA anti-tissue transglutaminase antibodies, and serum IL-8 levels were significantly increased in patients with DH. These studies demonstrate that patients with DH have evidence of endothelial cell activation in the skin and systemic manifestations of the ongoing inflammation associated with the mucosal immune response. Endothelial cell activation may play a critical role in the development of skin lesions in patients with DH and may represent a common mechanism for cutaneous manifestations of inflammatory gastrointestinal diseases.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Dermatitis Herpetiformis; E-Selectin; Endothelial Cells; Female; Gastroenteritis; GTP-Binding Proteins; Humans; Immunoglobulin A; Intercellular Adhesion Molecule-1; Interleukin-8; L-Selectin; Male; Middle Aged; Protein Glutamine gamma Glutamyltransferase 2; RNA, Messenger; Skin; Transglutaminases; Tumor Necrosis Factor-alpha

Early identification of the pathogen causing acute gastroenteritis in children helps the physicians managing the disease and prevents unnecessary antibiotic treatment. C-reactive protein (CRP), interleukin (IL) 6 and IL-8 play a major role in immune responses and have been studied in a large number of infectious and noninfectious inflammatory diseases. The purpose of this study was to determine the serum IL-6 and IL-8 concentrations early in the course of acute gastroenteritis to see if these cytokines were useful diagnostic markers in differentiating viral from bacterial gastroenteritis.. Interleukin 6, IL-8 and CRP were measured in 18 patients with bacterial gastroenteritis, 21 patients with viral gastroenteritis and 17 healthy children.. Interleukin 6 and CRP concentrations in patients with bacterial gastroenteritis were significantly higher than those in patients with viral gastroenteritis and healthy controls (P < 0.001). IL-8 concentrations in patients with viral and bacterial gastroenteritis were both increased and were not statistically different. IL-6 and IL-8 levels had diagnostic sensitivities of 79% and 50% and specificities of 86% and 67%, respectively. The combination of IL-6 and CRP had a sensitivity of 94%, specificity of 71%, a positive predictive value of 74% and a negative predictive value of 93.75%.. Serum IL-6 may be a useful marker for early differentiation of viral and bacterial gastroenteritis in children, especially in combination with CRP.

Topics: Acute Disease; Biomarkers; C-Reactive Protein; Case-Control Studies; Child, Preschool; Dysentery, Bacillary; Enzyme-Linked Immunosorbent Assay; Female; Gastroenteritis; Humans; Infant; Interleukin-6; Interleukin-8; Male; Rotavirus Infections; Salmonella Infections; Sensitivity and Specificity; Yersinia Infections

Knowledge about the origin and identity of the microbial products recognized by the innate immune system is important for understanding the pathogenesis of inflammatory diseases. We investigated the potential role of Salmonella enterica serotype Typhimurium fimbriae as pathogen-associated molecular patterns (PAMPs) that may stimulate innate pathways of inflammation. We screened a panel of 11 mutants, each carrying a deletion of a different fimbrial operon, for their enteropathogenicity using the calf model of human gastroenteritis. One mutant (csgBA) was attenuated in its ability to elicit fluid accumulation and GROalpha mRNA expression in bovine ligated ileal loops. The mechanism by which thin curled fimbriae encoded by the csg genes contribute to inflammation was further investigated using tissue culture. The S. Typhimurium csgBA mutant induced significantly less IL-8 production than the wild type in human macrophage-like cells. Purified thin curled fimbriae induced IL-8 expression in human embryonic kidney (HEK293) cells transfected with Toll-like receptor (TLR) 2/CD14 but not in cells transfected with TLR5, TLR4/MD2/CD14 or TLR11. Fusion proteins between the major fimbrial subunit of thin curled fimbriae (CsgA) and glutathione-S-transferase (GST) elicited IL-8 production in HEK293 cells transfected with TLR2/CD14. Proteinase K treatment abrogated IL-8 production elicited in these cells by GST-CsgA, but not by synthetic lipoprotein. GST-CsgA elicited more IL-6 production than GST in bone marrow-derived macrophages from TLR2+/+ mice, while there was no difference in IL-6 secretion between GST-CsgA and GST in macrophages from TLR2-/- mice. These data suggested that CsgA is a PAMP that is recognized by TLR2.

Topics: Adhesins, Bacterial; Animals; Cattle; Cell Line; Chemokine CXCL1; Chemokines; Chemotactic Factors; Disease Models, Animal; Fimbriae, Bacterial; Gastroenteritis; Gene Deletion; Genes, Bacterial; Humans; Ileum; Intercellular Signaling Peptides and Proteins; Interleukin-6; Interleukin-8; Operon; RNA, Messenger; Salmonella enterica; Toll-Like Receptor 2

The involvement of the proinflammatory cytokines, interleukin 8 (IL-8) and 6 (IL-6), was studied during the first 72 h of acute invasive gastroenteritis. Study population included 33 infants and young children aged six months to six years and seven age-matched controls. As a group, patients with acute invasive gastroenteritis had an increased serum level of IL-8 and IL-6 as compared with healthy controls (p < 0.002 and p < 0.001, respectively). Subjects were then divided into two groups based on stool cultures (proven and non-proven bacterial cultures). Patients with bacterial-proven acute invasive gastroenteritis tended to have increased IL-8 serum concentrations (p < 0.07) as compared with those with non-proven bacterial etiologies and IL-6 levels were only detected in subjects with positive bacterial cultures (p < 0.05). When dividing each sub-group into early and late blood drawing with respect to disease onset, no statistical differences were found in each group but subjects with bacterial-proven etiologies had significant higher IL-6 levels as compared with non-proven etiologies at the two time points (p < 0.019 and p < 0.015, respectively). In conclusion, the proinflammatory cytokines, IL-6 and IL-8, are involved in acute invasive gastroenteritis. The difference in IL-6, and to a lesser degree IL-8, between proven and non-proven bacterial etiologies, needs further investigation.

Topics: Child; Child, Preschool; Enterobacteriaceae; Enterobacteriaceae Infections; Gastroenteritis; Humans; Infant; Interleukin-6; Interleukin-8; Leukocyte Count; Neutrophils; Time Factors

There is increasing evidence that by facilitating translocation of Shiga toxin (Stx) across the intestinal epithelium and by transporting bound toxin to remote sites such as the renal endothelium, polymorphonuclear leukocytes (PMNs) play a key role in the pathogenesis of Shiga-toxigenic Escherichia coli (STEC) disease. Plasma levels of PMN-attracting CXC chemokines such as interleukin-8 (IL-8) also appear to correlate in humans with the severity of disease. Thus, the capacity of STEC strains to elicit CXC chemokine responses in intestinal epithelial cells may be a crucial step in pathogenesis. Accordingly, we attempted to determine which STEC factors are responsible for CXC chemokine induction in human colonic epithelial cells. Infection of Hct-8 cells with locus for enterocyte effacement (LEE)-negative STEC strains isolated from patients with severe STEC disease resulted in up-regulation of IL-8, macrophage inflammatory protein 2alpha (MIP-2alpha), MIP-2beta, and ENA-78 mRNA significantly higher and earlier than that elicited by several LEE-positive STEC strains, including the O157:H7 strain EDL933. Similarly, levels of IL-8 protein in LEE-negative STEC-infected Hct-8 culture supernatants were significantly higher than in LEE-positive STEC-infected culture supernatants. The difference in responses could not be attributed to the expression or nonexpression of LEE genes, the presence or absence of an STEC megaplasmid, or differences in O serogroups or in the type or amount of Stx produced. Interestingly, however, several of the LEE-negative STEC strains eliciting the strongest chemokine responses belonged to flagellar serotype H21. Incubation of Hct-8 cells with isolated H21 flagellin elicited IL-8 and MIP-2alpha responses similar to those seen in the presence of the most potent LEE-negative STEC strains. Deletion of the fliC gene, but not the stx(2) gene, largely abolished the capacity of O113:H21 LEE-negative STEC strain 98NK2 to elicit IL-8 and MIP-2alpha responses in Hct-8 cells. Taken together, these data suggest that although Stx is capable of inducing CXC chemokine responses, the elevated responses seen in cells infected with certain STEC strains are largely attributable to the production of flagellin.

Topics: Base Sequence; Cell Line; Chemokines, CXC; Colon; DNA; Epithelial Cells; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Flagellin; Gastroenteritis; Genes, Bacterial; Humans; Interleukin-8; Mutation; Phosphoproteins; RNA, Messenger; Shiga Toxin 2; Up-Regulation; Virulence

The objective of this study was to identify parameters indicating a risk for developing typical haemolytic uremic syndrome (D+HUS) during the prodromal phase of diarrhea caused by enterohaemorrhagic Escherichia coli (EHEC). Forty-eight children were studied prospectively with regard to inflammatory serum factors on admission to hospital. Ten patients developed D+HUS (group I), 15 suffered from viral-gastroenteritis (group IIa) and 23 from other types of bacterial gastroenteritis (group IIb). Mean levels of IL-8 tended to be elevated in group I compared to groups IIa and IIb. Neopterin and IL-10 levels particularly were significantly decreased in HUS in comparison to both gastroenteritis groups. Low IL-10 levels indicate a substantial disregulation of the immune response in HUS, as IL-10 downregulates the pro-inflammatory response and suppresses pro-coagulant activity in experimental endotoxemia. Our results suggest low neopterin, high IL-8 and especially low IL-10 levels are indicators of a high risk for developing HUS.

Topics: Bacterial Infections; Biomarkers; C-Reactive Protein; Child; Child, Preschool; Cytokines; Gastroenteritis; Hemolytic-Uremic Syndrome; Humans; Inflammation; Interleukin-10; Interleukin-6; Interleukin-8; Reference Values; Risk Factors; Tumor Necrosis Factor-alpha; Virus Diseases

Interleukin-8 (IL-8) elaborated by monocytes and endothelial cells is a cytokine which is responsible for adhesion of leucocytes to vascular endothelium and migration of neutrophils into the cerebrospinal fluid (CSF) from the intravascular space. The inflammation in meningitis is elicited by the cytokine release from leucocytes which encounter micro-organisms in the arachnoid or subarachnoid space. In bacterial meningitis, tumour necrosis factor (TNF), IL-1 and IL-6 are produced vigorously, and initiate and augment the inflammation in the central nervous system. In this study, utilizing a quantitative immunometric sandwich enzyme immunoassay, the concentration of IL-8 was investigated in the CSF of patients with bacterial meningitis, patients with aseptic meningitis, and patients with gastroenteritis who served as controls. The IL-8 concentration was markedly higher in the CSF of patients with bacterial meningitis (224 +/- 2.57 pg/ml; mean +/- SD) than in the CSF of patients with aseptic meningitis (less than 30 pg/ml). The IL-8 level in the CSF of patients with aseptic meningitis did not differ from that in the CSF of the patients with gastroenteritis (less than 30 pg/ml). The augmented production of IL-8 in CSF may account for the inflammation in bacterial meningitis being more severe than that in aseptic meningitis.

Topics: Acute Disease; Child; Child, Preschool; Female; Gastroenteritis; Humans; Infant; Interleukin-8; Male; Meningitis, Aseptic; Meningitis, Bacterial