interleukin-8 and Mucositis

The currently used National Cancer Institute (NCI) adverse events criteria for mucosal barrier injury (MBI) are insufficient for use in children. We searched for objective, easily measurable indicators for MBI in children with cancer.. In children with acute myeloid leukemia, various MBI-related clinical and laboratory tests were investigated, reflecting clinical severity (NCI symptomatic adverse events criteria (gold standard), daily gut score (DGS)), inflammation (plasma and fecal interleukin-8 (IL-8), fecal calprotectin), enterocytic loss (plasma citrulline, ratio fecal human DNA/total DNA) and intestinal permeability (sugar absorption tests).. Intestinal MBI as detected by the NCI adverse events criteria was found in 55% of chemotherapy cycles, correlating well with the continuous DGS (n = 55, rho = 0.581; P < 0.001). Intestinal cell loss as measured by the ratio fecal human DNA/total DNA and plasma citrulline correlated well with both NCI criteria (n = 61, rho = 0.357, P = 0.005 resp. n = 58, rho = -0.482; P < 0.001) and DGS (n = 54, rho = 0.352, P = 0.009 resp. n = 55, rho = -0.625; P < 0.001). Plasma IL-8 correlated strongly to plasma citrulline (n = 46, rho = -0.627; P < 0.001).. MBI was reflected by parameters indicating inflammation (IL-8) and cell loss (plasma citrulline, ratio fecal human DNA/total DNA). We conclude that plasma citrulline might be a good parameter for MBI. Further studies are needed to show whether plasma citrulline can be used as a marker for MBI in future research.

Topics: Acute Disease; Adolescent; Amsacrine; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Carbohydrates; Cell Death; Child; Child, Preschool; Citrulline; Cytarabine; Daunorubicin; DNA; Enterocytes; Etoposide; Feces; Female; Humans; Infant; Interleukin-8; Intestinal Absorption; Leukemia, Myeloid; Leukocyte L1 Antigen Complex; Male; Mitoxantrone; Models, Biological; Mucositis; Stomatitis

Activation of toll-like receptor 4 (TLR4) has been shown to be a major influence on the inflammatory signalling pathways in intestinal mucositis (IM), as demonstrated by TLR4 knock-out mice. Pharmacological TLR4 inhibition has thus been postulated as a potential new therapeutic approach for the treatment of IM but specific TLR4 inhibitors have yet to be investigated. As such, we aimed to determine whether direct TLR4 antagonism prevents inflammation in pre-clinical experimental models of IM. The non-competitive and competitive TLR4 inhibitors, TAK-242 (10 µM) and IAXO-102 (10 µM), respectively, or vehicle were added to human T84, HT-29, and U937 cell lines and mouse colonic explants 1 h before the addition of lipopolysaccharide (LPS) (in vitro: 100 µg/mL; ex vivo: 10 µg/mL), SN-38 (in vitro: 1 µM or 1 nM; ex vivo: 2 µM), and/or tumour necrosis factor-alpha (TNF-α) (5 µg/mL). Supernatant was collected for human IL-8 and mouse IL-6 enzyme-linked immunosorbent assays (ELISAs), as a measure of inflammatory signalling. Cell viability was measured using XTT assays. Explant tissue was used in histopathological and RT-PCR analysis for genes of interest: TLR4, MD2, CD14, MyD88, IL-6, IL-6R, CXCL2, CXCR1, CXCR2. SN-38 increased cytostasis compared to vehicle (P < 0.0001). However, this was not prevented by either antagonist (P > 0.05) in any of the 3 cell lines. Quantitative histological assessment scores showed no differences between vehicle and treatment groups (P > 0.05). There were no differences in in vitro IL-8 (P > 0.05, in all 3 cells lines) and ex vivo IL-6 (P > 0.05) concentrations between vehicle and treatment groups. Transcript expression of all genes was similar across vehicle and treatment groups (P > 0.05). TLR4 antagonism using specific inhibitors TAK-242 and IAXO-102 was not effective at blocking IM in these pre-clinical models of mucositis. This work indicates that specific epithelial inhibition of TLR4 with these compounds is insufficient to manage mucositis-related inflammation. Rather, TLR4 signalling through immune cells may be a more important target to prevent IM.

Topics: Animals; Humans; Inflammation; Interleukin-6; Interleukin-8; Irinotecan; Lipopolysaccharides; Mice; Mucositis; Toll-Like Receptor 4; U937 Cells

Irradiation, which affects cytokine secretion, is used to treat cancer patients. Cytokine levels have correlations to disease parameters, serving as biomarkers for patients. We aim to explore the effect of irradiation on cytokine production both in vitro (using lymphocytes from healthy donors) and in vivo (using serum levels of head and neck cancer patients following irradiation) and correlating them to mucositis severity/need for percutaneous endoscopic gastroscopy (PEG) tube installation.. Cytokine production by cultured lymphocytes from healthy donors, in vitro, following irradiation of 5 or 10 Gy. In addition, blood from 23 patients with head and neck cancers, irradiated by 60-72G in vivo, were assessed for inflammatory cytokines (tumor necrosis factor (TNF)α, interleukin (IL)-6, IL-8, IL-18), the anti-inflammatory cytokine IL-10, and the general marker sIL-2R. Following radiation, selected patients who were developing mucositis were treated by PEG tube installation. Changes in cytokine levels were studied as predictive biomarkers of response to therapy/PEG tube installation. Cytokine production levels were measured using ELISAs kits.. Irradiation decreased the levels of all tested cytokines, most notably IL-6 and IL-8, proportional to irradiation dose. In patients, increases in cytokine levels, correlated with mucositis severity and potentially the need for PEG tube installation.. Irradiation decreased the levels of all cytokines of healthy lymphocytes in a dose-dependent manner, especially those of IL-6 and IL-8. This study shows a correlation between high and increasing levels of inflammatory cytokines, sIL-2R, plus radiation toxicity and the need for PEG. The reduction of cytokine levels after radiotherapy predicts that PEG will not be required. Thus, our study shows that cytokine changes are predictive biomarkers in head and neck cancer patients.

Topics: Biomarkers; Cytokines; Head and Neck Neoplasms; Humans; Interleukin-6; Interleukin-8; Mucositis; Tumor Necrosis Factor-alpha

Peri-implant mucositis and peri-implantitis cases increase in number with the increase of implant applications. Peri-implant mucositis and peri-implantitis are defined as inflammatory diseases with inflammation and loss in soft and hard tissue, similar to the other periodontal diseases. As observed in many diseases, genetic predisposition factors also affect the progress of periodontitis and peri-implantitis.. This study examines if there is any solid genetic predisposition causing periodontitis and peri-implantitis formation in Turkish patients.. In order to evaluate single nucleotide polymorphism (SNP), Interleukin-8 (IL-8) and N-formyl-L-methionyl-L-leucyl-phenylalanine (fMLP), playing a role in the chemotaxis of neutrophils, and Fc Gamma Receptor IIA (FcγRIIA) and Fc Gamma Receptor IIIA (FcγRIIIA), playing a role in the antigen-antibody complexes and phagocytosis, were selected. Thirty-two Turkish non-smoking subjects, having periodontitis, thirty-three Turkish non-smoking subjects, having peri-implantitis and thirty-three Turkish non-smoking healthy subjects were selected. In total 98 adults participated in our study. Collected saliva samples from the participants were used for DNA isolation. SNPs were determined in these subgroups of the study by means of genotype-specific polymerase chain reactions.. When IL-8 A-251T, FcγRIIa -H131 and FcγRIIIa -V158 polymorphism were evaluated, no significant difference was found between periodontitis, peri-implantitis and healthy groups. However, this study observed that fMLP Receptor (FPR1) gene polymorphism creates a significant difference in individuals at higher risk of periodontitis or peri-implantitis.. Results show that individuals with the G genotype have a higher risk of periodontitis, while individuals with G / C genotype have higher risk of peri-implantitis.

Topics: Adult; Genetic Predisposition to Disease; Humans; Interleukin-8; Mucositis; Peri-Implantitis; Periodontitis; Polymorphism, Single Nucleotide

Porphyromonas gingivalis and Tannerella forsythia secrete proteases, gingipains and KLIKK-proteases. In addition, T. forsythia produces a serpin (miropin) with broad inhibitory spectrum. The aim of this pilot study was to determine the level of expression of miropin and individual proteases in vivo in periodontal and peri-implant health and disease conditions. Biofilm and gingival crevicular fluid (GCF)/ peri-implant sulcular fluid (PISF) samples were taken from healthy tooth and implant sites (n = 10), gingivitis and mucositis sites (n = 12), and periodontitis and peri-implantitis sites (n = 10). Concentration of interleukin-8 (IL-8), IL-1β and IL-10 in GCF was determined by enzyme-linked immunosorbent assay. Loads of P. gingivalis and T. forsythia and the presence of proteases and miropin genes were assessed in biofilm by quantitative PCR, whereas gene expression was estimated by quantitative RT-PCR. The presence of P. gingivalis and T. forsythia, as well as the level of IL-8 and IL-1β, were associated with disease severity in the periodontal and peri-implant tissues. In biofilm samples harboring T. forsythia, genes encoding proteases were found to be present at 72.4% for karilysin and 100% for other KLIKK-protease genes and miropin. At the same time, detectable mRNA expression of individual genes ranged from 20.7% to 58.6% of samples (for forsylisin and miropsin-1, respectively). In comparison with the T. forsythia proteases, miropin and the gingipains were highly expressed. The level of expression of gingipains was associated with those of miropin and certain T. forsythia proteases around teeth but not implants. Cumulatively, KLIKK-proteases and especially miropin, might play a role in pathogenesis of both periodontal and peri-implant diseases.

Topics: Bacterial Proteins; Biofilms; Biomarkers; Dental Implants; Gene Expression Regulation, Bacterial; Genes, Bacterial; Gingival Crevicular Fluid; Gingivitis; Humans; Interleukin-10; Interleukin-1beta; Interleukin-8; Mucositis; Peptide Hydrolases; Peri-Implantitis; Periodontitis; Pilot Projects; Porphyromonas gingivalis; Protease Inhibitors; RNA, Messenger; Serpins; Sweden; Tannerella forsythia

Chemotherapy-induced gastrointestinal (GI) toxicity is a common adverse effect of cancer treatment. We used preweaned piglets as models to test our hypothesis that the immunomodulatory and GI trophic effects of bovine colostrum would reduce the severity of GI complications associated with doxorubicin (DOX) treatment. Five-day-old pigs were administered DOX (1 × 100 mg/m(2)) or an equivalent volume of saline (SAL) and either fed formula (DOX-Form, n = 9, or SAL-Form, n = 7) or bovine colostrum (DOX-Colos, n = 9, or SAL-Colos, n = 7). Pigs were euthanized 5 days after initiation of chemotherapy to assess markers of small intestinal function and inflammation. All DOX-treated animals developed diarrhea, growth deficits, and leukopenia. However, the intestines of DOX-Colos pigs had lower intestinal permeability, longer intestinal villi with higher activities of brush border enzymes, and lower tissue IL-8 levels compared with DOX-Form (all P < 0.05). DOX-Form pigs, but not DOX-Colos pigs, had significantly higher plasma C-reactive protein, compared with SAL-Form. Plasma citrulline was not affected by DOX treatment or diet. Thus a single dose of DOX induces intestinal toxicity in preweaned pigs and may lead to a systemic inflammatory response. The toxicity is affected by type of enteral nutrition with more pronounced GI toxicity when formula is fed compared with bovine colostrum. The results indicate that bovine colostrum may be a beneficial supplementary diet for children subjected to chemotherapy and subsequent intestinal toxicity.

Topics: Animals; Animals, Newborn; Antibiotics, Antineoplastic; C-Reactive Protein; Cattle; Colostrum; Disease Models, Animal; Doxorubicin; Enteral Nutrition; Female; Humans; Infant Formula; Infant, Newborn; Inflammation Mediators; Interleukin-8; Intestinal Mucosa; Intestine, Small; Male; Microvilli; Mucositis; Nutritional Status; Permeability; Sus scrofa; Weight Gain

This study aimed to measure the levels of GM-CSF, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IFN-γ and TNF-α in peri-implant crevicular fluid (PICF) and saliva from patients with peri-implant disease.. Twenty two total edentulous patients were divided into two groups: Mucositis (MU) patients with bone loss around the implants until the first thread and pocket depth ≤3 mm, and Peri-implantitis (PI) patients with at least one implant with bone loss around two or more threads and pocket depth ≥4 mm. The clinical parameters evaluated were probing pocket depth, bleeding on probing, and percentage of plaque. PICF samples were collected from MU sites, and from shallow (SPI) and deep (DPI) sites in PI. Unstimulated whole and parotid duct saliva was collected from all patients. The cytokines were measured by a multiplexed immunoassay.. PI patients had a higher percentage of plaque compared with MU (P = 0.02). MU sites had lower pocket depth compared to SPI (P = 0.001) and to DPI (P ≤ 0.001). In PICF, the levels of IL-1β were significantly higher in SPI sites compared to MU (P = 0.03). In the saliva from parotid, IL-8 and IL-12 were significantly higher in patients with PI (P = 0.04).. Elevated levels of IL-1β in PICF seem to be a characteristic trait of patients with peri-implantitis. The parotid duct saliva showed a significant increase in expression of IL-8, which might be related to a systemic response.

Topics: Cytokines; Dental Plaque Index; Female; Gingival Crevicular Fluid; Humans; Interleukin-1beta; Interleukin-8; Male; Middle Aged; Mucositis; Peri-Implantitis; Periodontal Index; Saliva

5-Fluorouracil (5-FU) induces intestinal mucositis, which is characterized by epithelial ulcerations in the mucosa and clinical manifestations, such as pain and dyspeptic symptoms. Cytokines participate in the inflammatory and functional events of intestinal mucositis. IL-4 is an important mediator of intestinal inflammation, with either anti-inflammatory or pro-inflammatory functions, depending on the model of intestinal inflammation. This study aimed to evaluate the role of IL-4 in 5-FU-induced intestinal mucositis.. IL-4+/+ or IL-4-/- mice (25-30 g) were intraperitoneally injected with 5-FU (450 mg/Kg) or saline (C). After 3 days, the mice were sacrificed and the duodenum was evaluated for epithelial damage, MPO activity and cytokine concentration.. 5-FU induced significant damage in the intestinal epithelium of IL-4+/+ mice (reduction in the villus/crypt ratio: control=3.31±0.21 μm, 5-FU=0.99±0.10 μm). However, the same treatment did not induce significant damage in IL-4-/- mice (5-FU=2.87±0.19 μm) compared to wild-type mice. 5-FU-induced epithelial damage increased the MPO activity (neutrophil number) and the level of pro-inflammatory cytokines (IL-4, TNF-α, IL-1β and CXCL-8) in the duodenum. These results were not observed in IL-4-/- mice treated with 5-FU.. Our data suggest that IL-4 participates as a pro-inflammatory cytokine in a 5-FU-induced intestinal damage model and suggests that IL-4 antagonists may be novel therapeutics for this condition.

Topics: Animals; Antimetabolites, Antineoplastic; Duodenum; Fluorouracil; Interleukin-1beta; Interleukin-4; Interleukin-8; Intestinal Mucosa; Intestines; Mice; Mice, Inbred C57BL; Mice, Knockout; Mucositis; Tumor Necrosis Factor-alpha

The antiinflammatory agent curcumin (diferuloylmethane) has a potential to mitigate cancer therapy-induced mucositis. We assessed the in vitro extent of its bactericidal activity and determined the kinetics of its antiinflammatory effect on pharyngeal cells. Bactericidal activity was assessed using the LIVE/DEAD® Kit after 4 h of exposure to curcumin (50-200 μM) in 18 oropharyngeal species commonly associated with bacteremia in febrile neutropenia. Moraxella catarrhalis or its outer membrane vesicles were used to determine the inhibitory effect of curcumin on bacteria-induced proinflammatory activity as determined by cytokine release into the supernatant of Detroit 562 pharyngeal cells using the Luminex® xMAP® technology. Curcumin exerted a concentration-dependent bactericidal effect on all 18 species tested. After 4 h at 200 μM, 12 species tested were completely killed. Preincubation of Detroit cells with 200 μM curcumin for 5 to 60 min resulted in complete suppression of the release of tumor necrosis factor-α, interleukin (IL)-6, IL-8, monocyte chemoattractant protein 1, granulocyte macrophage-colony stimulating factor, and vascular endothelial growth factor. Fibroblast growth factor-2 and interferon-γ were not affected. Repetitive exposure to curcumin resulted in repetitive suppression of cytokine/chemokine expression lasting from 4 to 6 h. Through reduction of oral microbial density as well as suppression of inflammation cascades curcumin may prevent cancer therapy-induced oral mucositis, e.g., when applied as multiple daily mouth washes.

Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents; Bacteria; Biological Availability; Cell Line, Tumor; Chemokine CCL2; Curcumin; Epithelial Cells; Humans; Interleukin-6; Interleukin-8; Microbial Viability; Mucositis; Oral Health; Tumor Necrosis Factor-alpha

In this study, we evaluated C-reactive protein (CRP), interleukin (IL)-8, procalcitonin (PCT), and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) as predictors for bacterial infection in febrile neutropenia, plus their usefulness in febrile neutropenia during chemotherapy-induced gastrointestinal mucositis.. Plasma was obtained from pediatric oncology patients at presentation with febrile neutropenia (n = 43) and 24-48 h later (n = 17). The patients were classified as having or not having a bacterial infection. Plasma was also obtained of patients in the absence and in the presence of mucositis (n = 26).. At presentation with febrile neutropenia, median IL-8 and PCT levels were significantly increased in patients with a bacterial infection, in contrast to CRP and sTREM-1. IL-8 was the most sensitive marker for the early detection of bacterial infection, in combination with clinical parameters or PCT the sensitivity reached 100%. After 24-48 h, only PCT was significantly elevated during bacterial infection. IL-8 levels were significantly increased during mucositis. Mucositis did not cause considerable changes in PCT levels.. IL-8 is the most useful marker for the early detection of bacterial infections, compared with CRP, PCT, and sTREM-1. IL-8 in combination with clinical parameters or PCT might be even more useful. Gastrointestinal mucositis alone does not affect PCT levels, in contrast to IL-8 levels, and therefore, PCT might be more useful for the detection of bacterial infections during mucositis than IL-8.

Topics: Adolescent; Antineoplastic Agents; Bacterial Infections; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child; Female; Fever; Gastrointestinal Tract; Humans; Interleukin-8; Male; Membrane Glycoproteins; Mucositis; Neoplasms; Neutropenia; Prospective Studies; Protein Precursors; Receptors, Immunologic; Sensitivity and Specificity; Triggering Receptor Expressed on Myeloid Cells-1

Analysis of peri-implant crevicular fluid (PICF) offers a non-invasive means of studying the host response in peri-implant disease and may provide an early indication of patients at risk for active disease. This study examined the PICF levels of interleukin-1beta (IL-1beta), tumour necrosis factor alpha (TNF-alpha), interleukin-8 (IL-8) and macrophage inflammatory protein-1alpha (MIP-1alpha) in patients with non-manifesting inflammation, early and late stages of mucositis. The study group comprised 90 adult healthy volunteers with endosseal titanium implants inserted. Samples were taken from peri-implant sulcus using a filter paper technique. Implant tissues were categorized clinically as healthy, early mucositis or advanced mucositis. Clinical manifestations were determined by: gingival index and bleeding on probing, plaque index and radiographic analyses. Cytokine concentrations were assesed using commercially available enzyme-linked immunosorbent assay kits. Patients from the control group (healthy patients) have significantly lower concentrations of IL-1beta, TNF-alpha, IL-8 and MIP-1alpha in PICF compared with both groups with mucositis. Positive correlation was noted in the control group between IL-1beta and TNF-alpha and between MIP-1alpha and IL-8 in the group with early mucositis. The results suggest that cytokines could be prognostic markers of implant failure.

Topics: Chemokine CCL3; Cytokines; Dental Implantation, Endosseous; Dental Implants; Dental Restoration Failure; Female; Gingival Crevicular Fluid; Humans; Inflammation Mediators; Interleukin-1beta; Interleukin-8; Male; Middle Aged; Mucositis; Periodontal Index; Periodontitis; Stomatitis; Tumor Necrosis Factor-alpha

Topics: Biomarkers; Carbohydrates; Citrulline; DNA; Feces; Humans; Interleukin-8; Intestinal Absorption; Leukocyte L1 Antigen Complex; Models, Biological; Mucositis