Pediatric patients with inflammatory bowel disease exhibit increased serum levels of proinflammatory cytokines and chemokines, but decreased circulating levels of macrophage inhibitory protein-1β, interleukin-2 and interleukin-17

Kleiner, Giulio; Zanin, Valentina; Monasta, Lorenzo; Crovella, Sérgio; Caruso, Lorenzo; Milani, Daniela; Marcuzzi, Annalisa

doi:10.3892/etm.2015.2370

Cited by 13 publications

(14 citation statements)

References 39 publications

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“…However, it didn’t show a significant difference between UC patients and the controls in this study. The similar results were reported in pediatric patients with inflammatory bowel disease[ 42 ]. These results were completely unexpected, but may contribute to explain why certain IBD patient failed to benefit from anti-TNF therapy.…”

Section: Discussionsupporting

confidence: 89%

Short-Term Surveillance of Cytokines and C-Reactive Protein Cannot Predict Efficacy of Fecal Microbiota Transplantation for Ulcerative Colitis

Zhang

Cui

et al. 2016

PLoS ONE

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ObjectiveThere were no reports on predicting long-term efficacy of fecal microbiota transplantation (FMT) for ulcerative colitis (UC). This study aimed to detect short-term changes of cytokines and C-reactive protein (CRP) in patients with UC undergoing FMT, and to evaluate the predictive value of CRP and cytokines for the long-term efficacy of FMT.MethodsNineteen patients with moderate to severe UC (Mayo score ≥ 6) were treated with single fresh FMT through mid-gut. Serum samples were collected before and three days post-FMT. Clinical responses were evaluated by a minimum follow-up of three months. Patients with clinical improvement and remission at the assessment point of three-month were included as response group, while patients without clinical improvement or remission were included as non-response group. Serum concentrations of cytokines (IL-1β, IL-2, IL-4, IL-6, IL-10, IL-11, IL-17A, IFN-γ, TNF, TNFR-1, TNFR-2, MCP-1, G-CSF, GM-CSF) and CRP were assayed to predict the clinical response of FMT.ResultsIn total, 10.5% (2/19) of patients achieved clinical remission and 47.4% (9/19) achieved clinical improvement (Response group, including clinical remission and clinical improvement), 42.1% (8/19) failed to benefit from FMT (Non-response group). In both Response group and Non-response group, the level of CRP at three days after FMT didn’t show significant decrease compared with that before FMT (p>0.05). However, in Response group, CRP level at three months after FMT decreased significantly than that before FMT (p<0.05). Compared with healthy controls (n = 9), patients with UC showed a higher baseline level of serum IL-6, TNFR-2 and G-CSF, and a lower level of IL-2 and IL-4 (p<0.05). In both Response group and Non-response group, none of the eleven detectable cytokines showed a significant difference between the value at three days after FMT and that before FMT (p>0.05).ConclusionsPatients with moderate to severe UC presented a complex disorder of cytokines. However, the efficacy of FMT for UC might not be predicted by the short-term surveillance of cytokines and CRP.

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Section: Discussionsupporting

confidence: 89%

Short-Term Surveillance of Cytokines and C-Reactive Protein Cannot Predict Efficacy of Fecal Microbiota Transplantation for Ulcerative Colitis

Zhang

Cui

et al. 2016

PLoS ONE

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“…Interestingly, several cytokine concentrations (e.g. IFN-γ and TNF-α) measured during this interaction were similar to reported levels in serum of patients with IBD (53,54).…”

Section: T Cell Mediated Acute Inflammation Is Exacerbated By Scfa Lsupporting

confidence: 82%

Gut-Liver physiomimetics reveal paradoxical modulation of IBD-related inflammation by short-chain fatty acids

Trapečar

Communal

Velazquez

et al. 2019

Preprint

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Association between the microbiome, IBD and liver diseases are known, yet cause and effect remain elusive. By connecting human microphysiological systems of the gut, liver and circulating Treg/Th17 cells, we modeled progression of ulcerative colitis (UC) ex vivo. We show that microbiome-derived short-chain fatty acids (SCFA) may either improve or worsen disease severity, depending on the activation state of CD4 T cells. Employing multiomics, we found SCFA reduced innate activation of the UC gut and increased hepatic metabolism. However, during acute T cell-mediated inflammation, SCFA exacerbate CD4 T cell effector function leading to gut barrier disruption and liver damage. These paradoxical findings underscore the emerging utility of human physiomimetic technology to study causality and temporal facets of gut-liver axis related diseases where animal models leave ambiguity.

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“…Except for eotaxin, which has become a novel therapeutic target in UC [ 27 ], eosinophil-associated cytokines, such as GM-CSF, IL3, IL5, and IL13, have not been comprehensively analyzed in the context of IBD. Available data are scanty, mostly derived from the analysis of small cohorts, and obtained exclusively from multiplexed analyses intended for screening purposes, in which cytokines less abounded in sera frequently balance at the verge of lower detection limits of the tests, making their evaluation problematic [ 28 – 30 ]. Herein, the dilution of our samples was adjusted to enable credible analysis of these analytes.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic Potential of Systemic Eosinophil-Associated Cytokines and Growth Factors in IBD

Neubauer

Matusiewicz

Bednarz−Misa

et al. 2018

Gastroenterology Research and Practice

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Despite the acknowledged contribution of eosinophils to the disease pathogenesis, available data on cytokines closely related to the peripheral eosinophils in inflammatory bowel disease (IBD) are scattered. We assessed the concentrations of eosinophil-associated cytokines and growth factors in the group of 277 individuals (101 patients with Crohn's disease (CD), 77 with ulcerative colitis (UC), 16 with irritable bowel syndrome (IBS), and 83 healthy controls) and referred to IBD activity and the levels of hsCRP. As compared to IBS patients or healthy controls, patients with CD had significantly higher levels of IL5, IL8, IL12(p70), GM-CSF, and TNFα and patients with UC, the levels of eotaxin, IL4, IL5, IL8, IL12(p70), IL13, GM-CSF, and TNFα were also higher. As compared to CD patients, patients with UC had significantly higher levels of eotaxin, IL4, IL5, IL8, and IL1. In turn, the concentrations of hsCRP were significantly higher in CD than UC. Except for IL13, all cytokines and hsCRP positively correlated with CDAI. In UC, a positive correlation with MDAI was observed for hsCRP, GM-CSF, IL12(p70), and IFNγ and a negative one for IL8. The concentrations of hsCRP, GM-CSF, IFNγ, IL12(p70), and RANTES were higher in UC patients with active than inactive disease whereas those of IL8 and TNFα were significantly lower. Eotaxin, determined individually or in a panel with IFNγ and hsCRP, showed fair accuracy in differentiating CD from UC. If confirmed on a larger representation of IBS patients, IL8 might support differential diagnosis of organic and functional conditions of the bowel. GM-CSF, in turn, demonstrated to be an excellent indicator of bowel inflammation and may be taken into consideration as a noninvasive marker of mucosal healing. In summary, eosinophil-associated cytokines are elevated in IBD, more pronouncedly in UC, and may support the differential diagnosis of IBD and aid in monitoring of mucosal healing.

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Pediatric patients with inflammatory bowel disease exhibit increased serum levels of proinflammatory cytokines and chemokines, but decreased circulating levels of macrophage inhibitory protein-1β, interleukin-2 and interleukin-17

Cited by 13 publications

References 39 publications

Short-Term Surveillance of Cytokines and C-Reactive Protein Cannot Predict Efficacy of Fecal Microbiota Transplantation for Ulcerative Colitis

Short-Term Surveillance of Cytokines and C-Reactive Protein Cannot Predict Efficacy of Fecal Microbiota Transplantation for Ulcerative Colitis

Gut-Liver physiomimetics reveal paradoxical modulation of IBD-related inflammation by short-chain fatty acids

Diagnostic Potential of Systemic Eosinophil-Associated Cytokines and Growth Factors in IBD

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