Glucocorticoid sensitivity in inflammatory bowel disease

Sidoroff, Marianne; Kolho, Kaija‐Leena

doi:10.3109/07853890.2011.590521

Cited by 19 publications

(20 citation statements)

References 73 publications

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“…Glucocorticoid strongly suppresses COX-2 expression induced by inflammatory stimuli and has been used in the treatment of many hypoxia-occurred pathological states (Baschant et al 2012;Reuter et al 2012;Sidoroff and Kolho 2012). We have recently reported that dexamethasone represses both hypoxia-induced COX-2 and induction of GILZ is a key event in hypoxia-induced COX-2 inhibition by glucocorticoids (Lim et al 2014).…”

Section: Discussionmentioning

confidence: 97%

Red ginseng represses hypoxia-induced cyclooxygenase-2 through sirtuin1 activation

et al. 2015

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Section: Discussionmentioning

confidence: 97%

Red ginseng represses hypoxia-induced cyclooxygenase-2 through sirtuin1 activation

et al. 2015

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“…In paediatric patients the therapy is commenced with 1-2 mg/kg/day of prednisone equivalents (max 60 mg) and tapered off preferably during 10 weeks [6]. However, glucocorticoid dependency affects approximately 20-40% of the patients and prolonged steroid courses are often seen in clinical practice [8,9]. …”

Section: Introductionmentioning

confidence: 99%

Screening for adrenal suppression in children with inflammatory bowel disease discontinuing glucocorticoid therapy

Sidoroff

Kolho

2014

BMC Gastroenterol

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BackgroundPharmacological doses of corticoids may result in adrenal suppression but with individual sensitivity. In paediatric inflammatory bowel disease (IBD), glucocorticoids are needed in the majority of the patients but there are less studies related to tapering off the drugs. The objective of this study was to estimate the frequency of adrenal insufficiency in children with IBD that were at the end of their systemic glucocorticoid therapy course.MethodsThe study was a retrospective case series of 59 consecutive paediatric IBD patients (median age 14.1 years; Crohn’s disease n = 22, ulcerative colitis n = 26, unclassified colitis n = 11) that were on oral prednisolone therapy about to be discontinued. The study patients were treated in a tertiary university hospital setting. Serum morning cortisol was measured with Immulite 2000 cortisol kit. Values < 20 nmol/l are undetectable and indicate adrenal suppression, values > 69 nmol/l are considered to represent normal basal secretion.ResultsThe morning cortisol was below the reference range in 20% of the patients and undetectable in 10%. Low cortisol levels associated with higher daily glucocorticoid doses (median 7.2 mg/m2 vs. 3.0 mg/m2 in patients with normal cortisol levels, p < 0.05) and with the long duration of the treatment (median 11 months vs. 4 months, p < 0.05). Patients with undetectable cortisol levels recovered within few weeks (median 5.6 weeks).ConclusionsIn paediatric IBD prolonged courses of glucocorticoids are frequent due to the steroid-dependent nature of the disease in a considerable proportion of patients. Adrenal suppression may occur in at least one fifth of the patients despite slowly tapering off the glucocorticoids. Notably, this is based on a set of serum cortisol measurements by request of experienced clinicians. All paediatric IBD patients receiving conventional doses of oral glucocorticoids should be subjected to screening for adrenal suppression when anticipated discontinuation of the drug.

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“…GCs play a critical role in the treatment of inflammatory bowel disease (IBD), including both ulcerative colitis (UC) and Crohn's Disease (CD), where they are used to induce remission in patients with moderate to severe disease 1, 2 . Although GCs have a long history of use, many patients do not adequately respond to treatment 3-5 and require alternative medical therapies and/or surgery. A prospective cohort study following CD patients through a course of the synthetic GC prednisolone found that 20% of patients were GC resistant (no regression of symptoms) and 59% of patients required surgery within 1 month of initiating GC therapy 6 .…”

Section: Introductionmentioning

confidence: 99%

“…In one study the rate of GC resistance in severe disease (42%) was only slightly larger than that in moderate disease (35%) 14 . Few, if any, predictors of clinical response to GCs exist in IBD 5 . Biomarkers that could identify GC response in patients before treatment would improve IBD management.…”

Section: Introductionmentioning

confidence: 99%

In vitro sensitivity assays and clinical response to glucocorticoids in patients with inflammatory bowel disease

Maranville

Micic

Hanauer

et al. 2014

Journal of Crohn's and Colitis

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Background Glucocorticoids (GCs) are steroid hormones used to induce remission in moderate-to-severe inflammatory bowel disease (IBD). A substantial fraction of patients do not respond to GC treatment and require alternate therapies or surgery. At present, non-response can only be assessed empirically by observing continued disease activity. Methods To identify potential biomarkers of GC response, we retrospectively identified and recruited 18 GC-responsive and 18 GC-nonresponsive IBD patients. This sample included 14 patients with ulcerative colitis (UC) and 22 patients with Crohn's disease (CD), all previously treated with steroids. In peripheral blood mononuclear cells from each patient, we performed in vitro assays to measure GC inhibition of three different immune stimulants (phytohemagglutinin [PHA], α-CD3/α-CD28, and lipopolysaccharide [LPS]). Results In both diseases, we found that inhibition of PHA-mediated T cell proliferation was significantly associated with clinical GC response (P=0.04). Inhibition of proliferation due to direct T cell receptor stimulation using α-CD3/α-CD28 was also significantly associated with clinical GC response in UC patients (P=0.009), but not in CD patients (P=0.78). Interestingly, inhibition of LPS-mediated cytokine secretion showed the strongest association with clinical GC response across both diseases (P=0.005). Conclusions We show that inhibition of LPS stimulation is more strongly associated with clinical GC response in IBD patients than inhibition of PHA and α-CD3/α-CD28-mediated proliferation. These results support an important role of bacterial recognition and innate immunity in the etiology of IBD. This assay could be a powerful predictor of clinical response to GCs.

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Glucocorticoid sensitivity in inflammatory bowel disease

Cited by 19 publications

References 73 publications

Red ginseng represses hypoxia-induced cyclooxygenase-2 through sirtuin1 activation

Red ginseng represses hypoxia-induced cyclooxygenase-2 through sirtuin1 activation

Screening for adrenal suppression in children with inflammatory bowel disease discontinuing glucocorticoid therapy

In vitro sensitivity assays and clinical response to glucocorticoids in patients with inflammatory bowel disease

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