interleukin-8 has been researched along with Clostridium-Infections* in 7 studies
1 review(s) available for interleukin-8 and Clostridium-Infections
1 trial(s) available for interleukin-8 and Clostridium-Infections
6 other study(ies) available for interleukin-8 and Clostridium-Infections
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Novel Biomarkers, Including
Traditional clinical models for predicting recurrent Clostridioides difficile infection do not perform well, likely owing to the complex host-pathogen interactions involved. Accurate risk stratification using novel biomarkers could help prevent recurrence by improving underutilization of effective therapies (i.e., fecal transplant, fidaxomicin, bezlotoxumab). We used a biorepository of 257 hospitalized patients with 24 features collected at diagnosis, including 17 plasma cytokines, total/neutralizing anti-toxin B IgG, stool toxins, and PCR cycle threshold ( Topics: Bacterial Toxins; Bayes Theorem; Biomarkers; Clostridioides difficile; Clostridium Infections; Endothelial Growth Factors; Epidermal Growth Factor; Humans; Interleukin-6; Interleukin-8; Polymerase Chain Reaction | 2023 |
Surface layer protein A from hypervirulent Clostridioides difficile ribotypes induce significant changes in the gene expression of tight junctions and inflammatory response in human intestinal epithelial cells.
Surface layer protein A (SlpA), the primary outermost structure of Clostridioides difficile, plays an essential role in C. difficile pathogenesis, although its interaction with host intestinal cells are yet to be understood. The aim of this study was to investigate the effects of SlpA extracted from C. difficile on tight junction (TJ) proteins expression and induction of pro-inflammatory cytokines in human colon carcinoma cell line HT-29. SlpA was extracted from three toxigenic C. difficile clinical strains including RT126, RT001, RT084 as well as C. difficile ATCC 700057 as non-toxigenic strain. Cell viability was performed by MTT assay, and the mRNA expression of TJ proteins and inflammation-associated genes was determined using quantitative RT-PCR. Additionally, the secretion of IL-8, IL-1β and TNF-α cytokines was measured by ELISA.. C. difficile SlpA from selected RTs variably downregulated the expression level of TJs-assassinated genes and increased the expression level of TLR-4 and pro-inflammatory cytokines in HT-29 treated cells. SlpA from RT126 significantly (p. The results of the present study highlighted the importance of SlpA in the pathogenesis of CDI and C. difficile-induced inflammatory response in the gut. Further studies are required to unravel the significance of the observed results in promoting the intestinal inflammation and immune response induced by C. difficile SlpA from different RTs. Topics: Bacterial Proteins; Clostridioides; Clostridioides difficile; Clostridium Infections; Epithelial Cells; Gene Expression; Humans; Inflammation; Interleukin-8; Ribotyping; Staphylococcal Protein A; Tight Junctions; Tumor Necrosis Factor-alpha | 2022 |
Oral Candida administration in a Clostridium difficile mouse model worsens disease severity but is attenuated by Bifidobacterium.
Gut fungi may influence the course of Clostridium difficile infection either positively or negatively for the host. Fungi are not prominent in the mouse gut, and C. albicans, the major human gastrointestinal commensal yeast, is in low abundance or absent in mice. Bifidobacterium is one of the probiotics that may attenuate the severity of C. difficile infection. Inflammatory synergy between C. albicans and C. difficile, in gut, may provide a state that more closely resembles human infection and be more suitable for testing probiotic effects. We performed fecal mycobiota analysis and administered C. albicans at 1 day prior to C. difficile dosing. Fecal eukaryotic 18S rDNA analysis demonstrated the presence of Ascomycota, specifically, Candida spp., after oral antibiotics, despite negative fecal fungal culture. C. albicans administration enhanced the severity of the C. difficile infection model as determined by mortality rate, weight loss, gut leakage (FITC-dextran assay), and serum and intestinal tissue cytokines. This occurred without increased fecal C. difficile or bacteremia, in comparison with C. difficile gavage alone. Candida lysate with C. difficile increased IL-8 production from HT-29 and Caco-2 human intestinal epithelial cell-lines. Bifidobacterium attenuated the disease severity of the C. difficile plus Candida model. The reduced severity was associated with decreased Candida burdens in feces. In conclusion, gut C. albicans worsened C. difficile infection, possibly through exacerbation of inflammation. Hence, a mouse model of Clostridium difficile infection with C. albicans present in the gut may better model the human patient condition. Gut fungal mycobiome investigation in patients with C. difficile is warranted and may suggest therapeutic targets. Topics: Administration, Oral; Animals; Bifidobacterium; Caco-2 Cells; Candida albicans; Clostridium Infections; Disease Models, Animal; Gastrointestinal Microbiome; HT29 Cells; Humans; Interleukin-8; Intestinal Mucosa; Male; Mice; Mice, Inbred C57BL; Mycobiome; Permeability; Probiotics | 2019 |
The presence of IL-8 +781 T/C polymorphism is associated with the parameters of severe Clostridium difficile infection.
There is large variation in the clinical manifestations of Clostridium difficile infection (CDI). We also still can not predict which patients are more susceptible to reinfection with CDI. The aim of our study was to evaluate the effect of gene single nucleotide polymorphisms (SNP) of proinflammatory cytokines, specifically IL-1β, IL-8 on the development, clinical course and recurrence of CDI.. We performed a prospective study of adults (130 people ≥ 18 years) including 65 patients with CDI treated in tertiary hospital and 65 healthy persons. The following 3 variants were analyzed for the occurrence of gene polymorphisms in patients with CDI versus the control group: IL-1β +3953 A/G (rs1143634), IL-1β -31 A/G (rs1143627), and IL-8 +781 T/C (rs2227306). Then, we assessed the correlation between these genetic polymorphisms and biochemical parameters important in CDI course, CDI severity as well as CDI recurrence.. The presence of genetic polymorphisms of IL-1β +3953 A/G, -31 A/G and IL-8 +781 T/C did not have an effect on the development or recurrence of CDI. The presence of IL-8 +781 T/C polymorphism is associated with the severe CDI. Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Clostridioides difficile; Clostridium Infections; Cytokines; DNA; Female; Humans; Interleukin-1beta; Interleukin-8; Male; Middle Aged; Poland; Polymorphism, Single Nucleotide; Prospective Studies; Recurrence | 2018 |
Successful therapy of Clostridium difficile infection with fecal microbiota transplantation.
Clostridium difficile infection (CDI) is the most common cause of infectious diarrhea and represents an important burden for healthcare worldwide. Symptoms of severe CDI include watery, foul-smelling diarrhea, peripheral leucocytosis, increased C-reactive protein (CRP), acute renal failure, hypotension and pseudomembranous colitis. Recent studies indicate that the main cause of CDI is dysbiosis, an imbalance in the normal gut microbiota. The restoration of a healthy gut microbiota composition via fecal microbiota transplantation (FMT) recently became more popular. The aim of the present study was to assess the effect of FMT on the healing of CDI and to analyze the changes in the level of pro-inflammatory markers (C-reactive protein, fecal calprotectin) and pro-inflammatory cytokines. Eighteen patients with CDI were included in our study (6 males and 12 females) with recurrent and/or severe CDI. The FMT was performed in 17 patients using colonoscopy, including 16 patients receiving a one-time FMT and 1 patient who needed 2 additional FMTs. One patient was treated with a single round of FMT using push-and-pull enteroscopy. In all CDI patients, before and 3 weeks after FMT, the following parameters were analyzed: C-reactive protein, fecal calprotectin, and plasma interleukin (IL)-6, IL-8 and IL-12, and tumor necrosis factor-alpha (TNF-α). In addition, the plasma level of LL-37, a cathelicidine peptide was assessed by fluorescence-activated cell sorting (FACS) before and 3 months after FMT. Finally, in 7 patients a microbiome analysis was performed by sequencing of 16SrRNA in stool probes obtained before and 3 weeks after FMT. The healing rate of CDI was 94%. In all successfully treated patients no recurrent CDI was observed during follow-up (16 months). The serum level of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-8 and IL-12) significantly decreased after FMT. Similarly, CRP and fecal calprotectin normalized after FMT. 3 months after FMT a significant increase of LL-37 in the plasma of successfully treated patients was monitored. The sequencing analysis demonstrated an elevated abundance of beneficial bacterial species such as Lactobacillaceae, Ruminococcaceae, Desulfovibrionaceae, Sutterellaceae and Porphyromonodacea after FMT. No serious side effects were observed. We concluded that FMT represented a very effective and safe treatment of recurrent and/or severe CDI and led to favorable shifts in the composition of gut microbiome. Topics: Aged; Anti-Bacterial Agents; C-Reactive Protein; Clostridioides difficile; Clostridium Infections; Colonoscopy; Diarrhea; Enterocolitis, Pseudomembranous; Fecal Microbiota Transplantation; Feces; Female; Gastrointestinal Microbiome; Humans; Inflammation; Interleukin-6; Interleukin-8; Male; Treatment Outcome; Tumor Necrosis Factor-alpha | 2016 |
Chondroitin sulfate proteoglycan 4 functions as the cellular receptor for Clostridium difficile toxin B.
As a gram-positive, spore-forming anaerobic bacillus, Clostridium difficile (C. difficile) is responsible for severe and fatal pseudomembranous colitis, and poses the most urgent antibiotic resistance threat worldwide. Epidemic C. difficile is the leading cause of antibiotic-associated diarrhoea globally, especially diarrhoea due to the emergence of hypervirulent strains associated with high mortality and morbidity. TcdB, one of the key virulence factors secreted by this bacterium, enters host cells through a poorly understood mechanism to elicit its pathogenic effect. Here we report the first identification of the TcdB cellular receptor, chondroitin sulfate proteoglycan 4 (CSPG4). CSPG4 was initially isolated from a whole-genome human shRNAmir library screening, and its role was confirmed by both TALEN- and CRISPR/Cas9-mediated gene knockout in human cells. CSPG4 is critical for TcdB binding to the cell surface, inducing cytoskeleton disruption and cell death. A direct interaction between the N-terminus of CSPG4 and the C-terminus of TcdB was confirmed, and the soluble peptide of the toxin-binding domain of CSPG4 could protect cells from the action of TcdB. Notably, the complete loss of CSPG4/NG2 decreased TcdB-triggered interleukin-8 induction in mice without significantly affecting animal mortality. Based on both the in vitro and in vivo studies, we propose a dual-receptor model for TcdB endocytosis. The discovery of the first TcdB receptor reveals a previously unsuspected role for CSPG4 and provides a new therapeutic target for the treatment of C. difficile infection. Topics: Animals; Antigens; Bacterial Proteins; Bacterial Toxins; Base Sequence; Clostridioides difficile; Clostridium Infections; Cytoskeleton; Endocytosis; Gene Knockout Techniques; HEK293 Cells; HeLa Cells; HT29 Cells; Humans; Interleukin-8; Mice; Mice, Inbred C57BL; Mice, Knockout; Protein Binding; Protein Structure, Tertiary; Proteoglycans; RNA, Small Interfering | 2015 |