A novel pathway by which the environmental toxin 4-Nonylphenol may promote an inflammatory response in inflammatory bowel disease

BackgroundAt present there are several kinds of medicine for treating acute gout arthritis (AGA). This study compared the efficacy and safety of prednisolone, etoricoxib, and indomethacin in the treatment of AGA.Material/MethodsThis was an open-label, randomized, active-comparator study in patients with AGA. Patients were randomized to 4 days of prednisolone 35 mg qd, etoricoxib 120 mg qd, or indomethacin 50 mg tid. The primary efficacy endpoint was the reduction of self-assessed pain in the index joint from baseline. Secondary endpoints included changes in physician’s assessment of tenderness, erythema, swelling, and joint activity; patient assessment of response to therapy; and safety.ResultsWe analyzed 113 patients. Baseline demographics were comparable among treatment groups. Oral prednisolone, etoricoxib, and indomethacin were similarly effective in improving pain, tenderness, and joint activity over 4 days. For inflammation, oral prednisolone, etoricoxib, and indomethacin were similarly effective in reducing erythema, but prednisolone might be more effective in reducing swelling than indomethacin. The patient response to therapy was similar in the 3 groups. There were more total adverse events with indomethacin compared with the other 2 drugs.ConclusionsEfficacy was comparable among prednisolone, etoricoxib, and indomethacin for the treatment of AGA. Prednisolone might be more effective in reducing inflammation and it had a better safety profile.

Section: Introductionmentioning

confidence: 99%

Comparison of Prednisolone, Etoricoxib, and Indomethacin in Treatment of Acute Gouty Arthritis: An Open-Label, Randomized, Controlled Trial

Liu

Guan

et al. 2016

“…Thus, it has been described as another plausible pathogenic factor in IBD. A recent experimental study revealed another potential pathogenetic factor of IBD; Kim et al found that in vitro, the administration of 4-nonylphenol up-regulates proinflammatory genes and decreases the expression of the anti-inflammatory genes in human cells lines, promoting gastrointestinal tract inflammation [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Inflammatory and Lipid-Associated Markers of Cardiovascular Diseases in Children with First Exacerbation of Inflammatory Bowel Disease

Pac-Kożuchowska

Krawiec

Mroczkowska-Juchkiewicz

et al. 2016

BackgroundAdult patients with inflammatory bowel disease (IBD) are at increased risk of early atherosclerosis and atherosclerosis-driven cardiovascular diseases. However, data on the development of early, subclinical atherosclerosis in children with IBD are scarce. The aim of this study was to assess selected biomarkers of atherosclerosis in children with IBD.Material/MethodsThe study group comprised 30 children with first exacerbation of IBD. Twenty healthy children were enrolled into the control group. Total cholesterol, triglycerides, low-density lipoproteins (LDL), high-density lipoproteins (HDL), lipoprotein (a) (Lp(a)), interleukin 6 (Il-6), high sensitivity C-reactive protein (hs-CRP), and oxidized LDL (ox LDL) were determined.ResultsThere were no significant differences in lipids profiles in IBD children and controls. Mean IL-6 level (8.996 pg/ml) was significantly higher in the IBD group compared to controls (3.502 pg/ml). Mean hs-CRP concentration was significantly higher in IBD children than in controls (7.648 and 1.290 μg/ml, respectively). In the IBD group, mean ox-LDL concentration (144.837 ng/ml) was lower than in controls (162.352 ng/ml), but the difference was non-significant (P=0.4). Mean Lp(a) serum level was higher in patients with IBD (19.418 mg/dl) than in controls (10.970 mg/dl), but it was also non-significant.ConclusionsNo significant differences were found in biomarkers of atherosclerosis in children with IBD compared to controls. Elevated IL-6 and hs-CRP level are well-established inflammatory markers. Further studies are needed to fully determine cardiovascular risk factors in IBD children.

“…However, it can be reasonably predicted that these genetic factors modify the intestinal epithelial cell barrier and have major effects on the function of innate and adaptive immune systems [ 18 ]. A wide variety of animal studies of mucosal inflammation that mimic IBD, as well as human IBD itself, strongly indicate the importance of Th1, Th2, and Th17 cells and their respective cytokines, as well as environmental toxins, in the development of this disease [ 19 – 21 ].…”

Section: Discussionmentioning

confidence: 99%

Elevated IL-23R Expression and Foxp3+Rorgt+ Cells in Intestinal Mucosa During Acute and Chronic Colitis

Yang

2016

BackgroundIL-23/IL-23R signaling plays a pivotal role during the course of inflammatory bowel diseases (IBD). However, the underlying mechanisms are poorly characterized. Foxp3+ regulatory T cells are critical in the maintenance of gut immune homeostasis and therefore are important in preventing the development of IBD. This study was performed to clarify the association between IL-23/IL-23R signaling and Foxp3+ regulatory T cells in colitis.Material/MethodsAcute and chronic mouse colitis models were established by administering mice DSS in drinking water. IL-23R, IL-23, IL-I7, and IFN-γ expression level, as well as regulatory T cell, Th17-, and Th1-related transcription factors Foxp3, RORγt, and T-bet were assayed by real-time PCR. The frequency of Foxp3+ RORγt+ cells in a Foxp3+ cell population in colon mucosa during acute and chronic colitis was evaluated through flow cytometry. The signaling pathway mediated by IL-23R in the colon mucosa from acute colitis mice and chronic colitis mice was monitored by Western blot analysis.ResultsWe detected elevated IL-23R, IL-23, and IFN-γ expression in colon mucosa during acute and chronic colitis and found increased IL-17 in acute colitis mice. Transcription factors Foxp3 and T-bet were elevated in colon mucosa during acute and chronic colitis. Phosphorylation of Stat3 was greatly enhanced, indicating the activation of IL-23R function in colitis mice. The percentage of Foxp3+ T cells in acute and chronic colitis mice was comparable to control mice, but there was a 2-fold increase of Foxp3+ RORγt+ cells among the Foxp3+ cell population in acute and chronic colitis mice compared to control mice.ConclusionsThese findings indicate that the induction of Foxp3+ RORγt+ T cells could be enhanced during inflammation in the intestine where IL-23R expression is greatly induced. Our study highlights the importance of IL-23R expression level and the instability of Foxp3+ regulatory T cells in the development of inflammatory bowel diseases.