Serum cytokine, chemokine, and growth factor profiles and their modulation in inflammatory bowel disease

Martínez‐Fierro, Margarita L.; Rocha-Pizaña, María del Refugio; Cardenas-Vargas, Edith; Cid-Baez, Miguel A; Trejo‐Vazquez, Fabiola; Flores‐Morales, Virginia; Villela-Ramirez, Gabriela A; Delgado‐Enciso, Iván; Rodríguez‐Sánchez, Iram P.; Ortiz-Castro, Yolanda

doi:10.1097/md.0000000000017208

Cited by 39 publications

(48 citation statements)

References 39 publications

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“…Patients with endoscopically active disease showed higher serum levels of granulocyte colonystimulating factor (G-CSF) (P = 0.04), IL-1 receptor antagonist (IL-1Ra) (P = 0.04), and platelet-derived growth factor BB (P = 0.02). Increased serum expression of interferon-induced protein 10 was associated with extraintestinal manifestations (arthritis) of IBD (P = 0.041) (163).…”

Section: Miscellaneous Indicatorsmentioning

confidence: 98%

Serum Biomarkers for Inflammatory Bowel Disease

et al. 2020

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Background: Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a chronic, inflammatory disorder of the gastrointestinal tract. As the novel therapeutic goal and biologicals are widely recognized, accurate assessment of disease and prediction of therapeutic response have become a crucial challenge in clinical practice. Also, because of the continuously rising incidence, convenient and economical methods of diagnosis and clinical assessment are urgently needed. Recently, serum biomarkers have made a great progress and become a focus in IBD study because they are non-invasive, convenient, and relatively inexpensive than are markers in biopsy tissue, stool, breath, and other body fluids. Aims: To review the available data on serological biomarkers for IBD. Methods: We searched PubMed using predefined key words on relevant literatures of serum biomarkers regarding diagnosis, evaluation of therapeutic efficacy, surveillance of disease activity, and assessment of prognosis for IBD. Results: We reviewed serological biomarkers that are well-established and widely used (e.g., C-reactive protein), newly discovered biomarkers (e.g., cytokines, antibodies, and non-coding RNAs), and also recently advancements in serological biomarkers (e.g., metabolomics and proteomics) that are used in different aspects of IBD management. Conclusions: With such a wealth of researches, to date, there are still no ideal serum biomarkers for IBD. Serum profiling and non-coding RNAs are just starting to blossom but reveal great promise for future clinical practice. Combining different biomarkers can be valuable in improving performance of disease evaluation.

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Section: Miscellaneous Indicatorsmentioning

confidence: 98%

Serum Biomarkers for Inflammatory Bowel Disease

et al. 2020

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“…From Vanderbilt University, Goldenring, et al examined the association between injury to the mucosae of the GI tract and emergence of metaplastic lineages as an active reparative response to ulceration [35]. The notion that UC and CC are histologically different suggests that DEFA5, and/or in association with DEFA5-induced signatures, suggests a link between DEFA5 and bacterial enterotoxins in the pathogenesis and differentiation of IBD [6,36]. It is unknown whether high levels of DEFA5 alone may be deleterious to intestinal tissues.…”

Section: Plos Onementioning

confidence: 99%

Linking bacterial enterotoxins and alpha defensin 5 expansion in the Crohn’s colitis: A new insight into the etiopathogenetic and differentiation triggers driving colonic inflammatory bowel disease

et al. 2021

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Evidence link bacterial enterotoxins to apparent crypt-cell like cells (CCLCs), and Alpha Defensin 5 (DEFA5) expansion in the colonic mucosa of Crohn’s colitis disease (CC) patients. These areas of ectopic ileal metaplasia, positive for Paneth cell (PC) markers are consistent with diagnosis of CC. Retrospectively, we: 1. Identified 21 patients with indeterminate colitis (IC) between 2000–2007 and were reevaluation their final clinical diagnosis in 2014 after a followed-up for mean 8.7±3.7 (range, 4–14) years. Their initial biopsies were analyzed by DEFA5 bioassay. 2. Differentiated ulcer-associated cell lineage (UACL) analysis by immunohistochemistry (IHC) of the CC patients, stained for Mucin 6 (MUC6) and DEFA5. 3. Treated human immortalized colonic epithelial cells (NCM460) and colonoids with pure DEFA5 on the secretion of signatures after 24hr. The control colonoids were not treated. 4. Treated colonoids with/without enterotoxins for 14 days and the spent medium were collected and determined by quantitative expression of DEFA5, CCLCs and other biologic signatures. The experiments were repeated twice. Three statistical methods were used: (i) Univariate analysis; (ii) LASSO; and (iii) Elastic net. DEFA5 bioassay discriminated CC and ulcerative colitis (UC) in a cohort of IC patients with accuracy. A fit logistic model with group CC and UC as the outcome and the DEFA5 as independent variable differentiator with a positive predictive value of 96 percent. IHC staining of CC for MUC6 and DEFA5 stained in different locations indicating that DEFA5 is not co-expressed in UACL and is therefore NOT the genesis of CC, rather a secretagogue for specific signature(s) that underlie the distinct crypt pathobiology of CC. Notably, we observed expansion of signatures after DEFA5 treatment on NCM460 and colonoids cells expressed at different times, intervals, and intensity. These factors are key stem cell niche regulators leading to DEFA5 secreting CCLCs differentiation ‘the colonic ectopy ileal metaplasia formation’ conspicuously of pathogenic importance in CC.

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“…10 Cytokine concentrations in patients with IBD have been reported in multiple publications. [23][24][25][26][27][28] The high degree of variability in the reported concentrations of these cytokines across different studies may likely be attributed to the different bioassay methods used.…”

Section: Discussionmentioning

confidence: 99%

“…1 There were a few instances in which cytokine concentrations were higher than 50 pg/mL, notably IL-8 and TNF-α; however, these higher concentrations were observed in both patients with UC or CD and healthy subjects. 25 Exposure to Conventional Medications. Comparable exposure in literature was reported following administration of conventional nonbiologic UC and CD medications metabolized via CYP3A between patients with UC or CD and healthy subjects (or patients with inactive IBD or in remission).…”

Section: Literature Data Reviewmentioning

confidence: 99%

Assessment of Vedolizumab Disease‐Drug‐Drug Interaction Potential in Patients With Inflammatory Bowel Diseases

Sun

Lirio

Schneider

et al. 2020

Clinical Pharm in Drug Dev

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Disease‐drug‐drug interactions (DDDIs) have been identified in some inflammatory diseases in which elevated proinflammatory cytokines can downregulate the expression of cytochrome P450 (CYP) enzymes, potentially increasing systemic exposure to drugs metabolized by CYPs. Following anti‐inflammatory treatments, CYP expression may return to normal, resulting in reduced drug exposure and diminished clinical efficacy. Vedolizumab has a well‐established positive benefit‐risk profile in patients with ulcerative colitis (UC) or Crohn's disease (CD) and has no known systemic immunosuppressive activity. A stepwise assessment was conducted to evaluate the DDDI potential of vedolizumab to impact exposure to drugs metabolized by CYP3A through cytokine modulation. First, a review of published data revealed that patients with UC or CD have elevated cytokine concentrations relative to healthy subjects; however, these concentrations remained below those reported to impact CYP expression. Exposure to drugs metabolized via CYP3A also appeared comparable between patients and healthy subjects. Second, serum samples from patients with UC or CD who received vedolizumab for 52 weeks were analyzed and compared with healthy subjects. Cytokine concentrations and the 4β‐hydroxycholesterol‐to‐cholesterol ratio, an endogenous CYP3A4 biomarker, were comparable between healthy subjects and patients both before and during vedolizumab treatment. Finally, a medical review of postmarketing DDDI cases related to vedolizumab from the past 6 years was conducted and did not show evidence of any true DDDIs. Our study demonstrated the lack of clinically meaningful effects of disease or vedolizumab treatment on the exposure to drugs metabolized via CYP3A through cytokine modulation in patients with UC or CD.

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Serum cytokine, chemokine, and growth factor profiles and their modulation in inflammatory bowel disease

Cited by 39 publications

References 39 publications

Serum Biomarkers for Inflammatory Bowel Disease

Serum Biomarkers for Inflammatory Bowel Disease

Linking bacterial enterotoxins and alpha defensin 5 expansion in the Crohn’s colitis: A new insight into the etiopathogenetic and differentiation triggers driving colonic inflammatory bowel disease

Assessment of Vedolizumab Disease‐Drug‐Drug Interaction Potential in Patients With Inflammatory Bowel Diseases

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