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See detailIncreased production of matrix metalloproteinase-3 and tissue inhibitor of metalloproteinase-1 by inflamed mucosa in inflammatory bowel disease
Louis, Edouard ULg; Ribbens, Clio ULg; Barreto Dos Santos, Amelia ULg et al

in Clinical & Experimental Immunology (2000), 120(2), 241-246

Inflammatory bowel diseases (IBD) are characterized by a sustained inflammatory cascade that gives rise to the release of mediators capable of degrading and modifying bowel wall structure. Our aims were ... [more ▼]

Inflammatory bowel diseases (IBD) are characterized by a sustained inflammatory cascade that gives rise to the release of mediators capable of degrading and modifying bowel wall structure. Our aims were (i) to measure the production of matrix metalloproteinase-3 (MMP-3), and its tissue inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1), by inflamed and uninflamed colonic mucosa in IBD, and (ii) to correlate their production with that of proinflammatory cytokines and the anti-inflammatory cytokine, IL-10. Thirty-eight patients with IBD, including 25 with Crohn's disease and 13 with ulcerative colitis, were included. Ten controls were also studied. Biopsies were taken from inflamed and uninflamed regions and inflammation was graded both macroscopically and histologically. Organ cultures were performed for 18 h. Tumour necrosis factor-alpha (TNF-alpha), IL-6, IL-1beta, IL-10, MMP-3 and TIMP-1 concentrations were measured using specific immunoassays. The production of both MMP-3 and the TIMP-1 were either undetectable or below the sensitivity of our immunoassay in the vast majority of uninflamed samples either from controls or from those with Crohn's disease or ulcerative colitis. In inflamed mucosa, the production of these mediators increased significantly both in Crohn's disease (P < 0.01 and 0.001, respectively) and ulcerative colitis (P < 0.001 and 0.001, respectively). Mediator production in both cases was significantly correlated with the production of proinflammatory cytokines and IL-10, as well as with the degree of macroscopic and microscopic inflammation. Inflamed mucosa of both Crohn's disease and ulcerative colitis show increased production of both MMP-3 and its tissue inhibitor, which correlates very well with production of IL-1beta, IL-6, TNF-alpha and IL-10. [less ▲]

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See detailTumour Necrosis Factor (Tnf) Gene Polymorphism in Crohn's Disease (Cd): Influence on Disease Behaviour?
Louis, Edouard ULg; Peeters, Marc; Franchimont, D. et al

in Clinical & Experimental Immunology (2000), 119(1), 64-8

Crohn's disease (CD) is a multifactorial disease with genetic heterogeneity. TNF-alpha plays a key role in the development of the mucosal lesions. The aim of our work was to study a single base pair ... [more ▼]

Crohn's disease (CD) is a multifactorial disease with genetic heterogeneity. TNF-alpha plays a key role in the development of the mucosal lesions. The aim of our work was to study a single base pair polymorphism located in the promoter region of TNF gene, in a large population of CD patients with well defined phenotypes. One hundred and ninety-three patients with CD and 98 ethnically matched controls were studied. The -308 single base pair polymorphism of TNF gene was studied using an allele-specific polymerase chain reaction. Genotype and allelic frequencies were compared between patients and controls and between subgroups of patients defined by sex, age at diagnosis, familial history, location of disease, type of disease, extra-intestinal manifestations, and response to steroid treatment. In 29 patients a measure of TNF-alpha production by colonic biopsies was performed. The frequency of the allele TNF2 as well as the proportion of carriers of the allele TNF2 were slightly but not significantly lower in CD than in controls (11.9% versus 14.8% and 21.5% versus 27.6%, respectively). A more prominent difference in frequencies of allele TNF2 and in proportions of TNF2 carriers was found when comparing subgroups of patients. The frequency of allele TNF2 was significantly higher in steroid-dependent than in non-steroid-dependent disease (28.1% versus 10.3%; Delta = 17.8%, 95% confidence interval (CI) = 6.3-29.5%, P = 0.0027) and tended to be higher in colonic than in small bowel disease and in fistulizing than in stricturing disease. Furthermore, TNF2 carriers tended to be more frequent in patients with steroid-dependent than non-steroid-dependent disease (43.8% versus 19.3%; Delta = 24.5%, 95% CI = 3.6-45.4%, P = 0.022), in patients with fistulizing than stricturing disease (26.5% versus 9.6%; Delta = 16.9%, 95% CI = 1. 1-32.6%, P = 0.036), and in patients with colonic than small bowel disease (26.5% versus 11.1%; Delta = 15.4%, 95% CI = -0.8-31.6%, P = 0.063). Finally, patients carrying at least one copy of allele 2 were found to produce slightly more TNF-alpha at the colonic level. The -308 TNF gene polymorphism may have a slight influence on the behaviour of CD. The carriage of allele 2 may favour steroid-dependent disease and to a lesser extent fistulizing and colonic disease, possibly secondary to a more intense TNF-alpha-driven inflammatory reaction at the mucosal level. [less ▲]

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See detailThe medical management of severe acute and chronic ulcerative colitis--current recommendations from the Belgian Working Group.
Melange, M.; D'Haens, G.; Devos, Martine ULg et al

in Acta Gastro-Enterologica Belgica (2000), 63(3), 273-4

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See detailTraitement médical des colites aiguës inflammatoires sévères
Belaiche, Jacques ULg; Louis, Edouard ULg

in Hépato-Gastro (2000), 7

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See detailInitial Medical Management of Severe Acute Ulcerative Colitis
Belaiche, Jacques ULg; Louis, Edouard ULg

in Acta Gastro-Enterologica Belgica (2000), 63(3, Jul-Sep), 275-8

Severe colitis is life-threatening complication of ulcerative colitis. Early recognition of the severity of the colitis, intensive medical therapy and prompt surgery when necessary have all contributed to ... [more ▼]

Severe colitis is life-threatening complication of ulcerative colitis. Early recognition of the severity of the colitis, intensive medical therapy and prompt surgery when necessary have all contributed to improved outcome. Initial medical treatment should be instituted as soon as the diagnosis is made with an intravenous corticosteroid associated with supportive treatment. If the patient fails to response to this intensive treatment after 5-7 days, cyclosporin should be initiated. If cyclosporin is not used then colectomy should be performed immediately. Moreover, significant deterioration at any point during medical therapy is an indication for colectomy. The gravity of the patient's condition require close interaction between physician an surgeon. [less ▲]

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See detailGenetics of Crohn's Disease Behaviour
Louis, Edouard ULg; Belaiche, Jacques ULg

in Acta Gastro-Enterologica Belgica (2000), 63(4, Oct-Dec), 377-9

Crohn's disease is probably an heterogeneous entity. This heterogeneity may be linked to either genetics or environment. In particular the behaviour of the disease, i.e. the tendency to develop ... [more ▼]

Crohn's disease is probably an heterogeneous entity. This heterogeneity may be linked to either genetics or environment. In particular the behaviour of the disease, i.e. the tendency to develop stricturing and/or penetrating lesions, may be linked to the genetic background. While epidemiological and clinical data suggest the relevance of these behavioural classifications, the progresses in the characterization of the immuno-inflammatory reaction in the bowel wall shed a new light on possible candidate genes for these genetic predispositions to various Crohn's disease behaviours. Association studies an linkage analysis focusing on growth factors, metalloproteinases and their tissue inhibitors as well as cytokines may bring new interesting data in this field. [less ▲]

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See detailReflux gastro-oesophagien et asthme
Lamproye, Anne ULg; Louis, Edouard ULg; Louis, Renaud ULg et al

in Revue Médicale de Liège (1999), 54(10), 805-8

Gastro-oesophageal reflux (GER) is more frequent in asthmatic patients than in the community at large. A causative association between the two diseases is suspected. Twenty-four hour ambulatory ... [more ▼]

Gastro-oesophageal reflux (GER) is more frequent in asthmatic patients than in the community at large. A causative association between the two diseases is suspected. Twenty-four hour ambulatory intraoesophageal pH monitoring represents the golden standard for the diagnosis of GER. The medical and/or surgical treatment of reflux in asthmatic patients with GER can improve pulmonary symptoms and to a lesser extent pulmonary function. The selection of the patients who will benefit from a GER treatment is difficult. Some symptoms like intrinsic asthma, nocturnal crises, could predict a good response to GER treatment. [less ▲]

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See detailAcute Lower Gastrointestinal Bleeding in Crohn's Disease: Characteristics of a Unique Series of 34 Patients. Belgian Ibd Research Group
Belaiche, Jacques ULg; Louis, Edouard ULg; D'Haens, Geert et al

in American Journal of Gastroenterology (1999), 94(8), 2177-81

OBJECTIVE: Acute lower gastrointestinal bleeding is a rare complication of Crohn's disease, which represents a diagnostic and therapeutic challenge. The aim of this study was to define epidemiological ... [more ▼]

OBJECTIVE: Acute lower gastrointestinal bleeding is a rare complication of Crohn's disease, which represents a diagnostic and therapeutic challenge. The aim of this study was to define epidemiological characteristics and therapeutic options of hemorrhagic forms of Crohn's disease. METHODS: Thirty-four cases of hemorrhagic forms of Crohn's disease were studied retrospectively. Acute lower gastrointestinal hemorrhage was defined as acute rectal bleeding originating in diseased bowel and requiring a transfusion of at least 2 units of red blood cells within 24 h. Upper gastrointestinal tract hemorrhage or anal lesions and postoperative bleeding were excluded. RESULTS: Mean age at time of hemorrhage was 34.2 +/- 14 yr. Mean duration of disease before the hemorrhage was 5.6 +/- 6 yr. The hemorrhage occurred during a flare up of the disease in 35% of cases. The hemorrhage revealed Crohn's disease in 23.5% of cases. The hemorrhage was more frequent in colonic disease (85%) than in isolated small bowel disease (15%) (p < 0.0001). The origin of bleeding was identified in 65% of cases, by colonoscopy (60%), by angiography (3 patients), or at surgery (1 patient). The bleeding lesion was an ulcer in 95% of cases, most often in the left colon. The treatment was surgical in 20.5% (colectomy in 36%), endoscopical (7 patients, including 5 successes), or medical. Hemorrhage recurred in 12 patients (35%) within a mean time of 3 yr (4 days-8 yr), requiring surgery in 3 cases. No death was observed. CONCLUSIONS: This study performed in a series characterized by a nonsurgical recruitment, the largest to date, shows that hemorrhagic forms of Crohn's disease may reveal disease in 23.5%, occurs in quiescent Crohn's disease in two-thirds of cases. Given the potential efficacy of endoscopical or medical treatment, as well as the absence of mortality, a conservative approach may be suggested as first-line therapy in the majority of patients. [less ▲]

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See detailTumor Necrosis Factor Alpha Decreases, and Interleukin-10 Increases, the Sensitivity of Human Monocytes to Dexamethasone: Potential Regulation of the Glucocorticoid Receptor
Franchimont, Denis; Martens, Henri ULg; Hagelstein, Marie-Thérèse ULg et al

in Journal of Clinical Endocrinology and Metabolism (1999), 84(8), 2834-9

Resistance to glucocorticoid therapy has been observed in patients with autoimmune/inflammatory diseases and may be related to the inflammatory process itself. The aim of this study was to examine the ... [more ▼]

Resistance to glucocorticoid therapy has been observed in patients with autoimmune/inflammatory diseases and may be related to the inflammatory process itself. The aim of this study was to examine the ability of tumor necrosis factor alpha (TNFalpha, a proinflammatory cytokine) and interleukin (IL)-10 (an anti-inflammatory cytokine) to differentially regulate the sensitivity of human monocytes/macrophages to glucocorticoids. To accomplish this, we first analyzed the pattern of TNFalpha and IL-10 inhibition by dexamethasone in LPS-stimulated whole-blood cell cultures. Second, we studied the modulation of the sensitivity of these cells to dexamethasone by preincubation with TNFalpha or IL-10 and measurement of LPS-stimulated IL-6 secretion. In addition, we evaluated the effect of dexamethasone on phorbolmyristate-acetate-stimulated IL-1 receptor antagonist secretion by the human monocytic cell line U937. Finally, we investigated whether the modulation of corticosensitivity in TNFalpha- and IL-10-pretreated U937 cells was related to a change of the glucocorticoid receptor concentration and affinity. Dexamethasone had different effects on LPS-induced TNFalpha and IL-10 secretion; whereas it suppressed TNFalpha in a dose-dependent fashion, its effect on IL-10 secretion was biphasic, producing stimulation at lower, and inhibition at higher doses. The concentration of LPS employed influenced the effect of dexamethasone on IL-10 secretion (P < 0.001). Pretreatment with TNFalpha diminished, and with IL-10 improved, the ability of dexamethasone to suppress IL-6 secretion in whole-blood cell cultures (P < 0.01 for both) and to enhance IL-1 receptor antagonist secretion by U937 cells (P < 0.05 for both). TNFalpha decreased (P < 0.001), while IL-10 increased (P < 0.001), the concentration of dexamethasone binding sites in these cells, with no discernible effect on their binding affinity. We conclude that glucocorticoids differentially modulate TNFalpha and IL-10 secretion by human monocytes in a LPS dose-dependent fashion and that the sensitivity of these cells to glucocorticoids is altered by TNFalpha or IL-10 pretreatment; TNFalpha blocks their effects, whereas IL-10 acts synergistically with glucocorticoids. This is accompanied by opposite glucocorticoid receptor changes, respectively opposing and favoring glucocorticoid actions. This study suggests that the pattern of pro-/antiinflammatory cytokine secretion may alter the response of patients to glucocorticoid therapy. [less ▲]

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See detailUse of the Enteroscope for Colo-Ileoscopy: Low Yield in Unexplained Lower Gastrointestinal Bleeding
Belaiche, Jacques ULg; Van Kemseke, Catherine ULg; Louis, Edouard ULg

in Endoscopy (1999), 31(4), 298-301

BACKGROUND AND STUDY AIMS: The small intestine is a potential origin of bleeding in patients with unexplained gastrointestinal tract hemorrhage or iron-deficiency anemia. Most reports on the investigation ... [more ▼]

BACKGROUND AND STUDY AIMS: The small intestine is a potential origin of bleeding in patients with unexplained gastrointestinal tract hemorrhage or iron-deficiency anemia. Most reports on the investigation of these patients describe the use of upper tract enteroscopy. The diagnostic yield of combined upper and lower enteroscopy has not been widely assessed and remains to be clarified. The aim of this study was to assess the benefit of lower gastrointestinal tract enteroscopy in occult digestive bleeding. PATIENTS AND METHODS: Between 1 December 1995 and 15 January 1998, 54 patients with gastrointestinal bleeding of unknown origin were prospectively studied using upper and lower video push enteroscopy (44 for chronic iron-deficiency anemia and 10 for unexplained gastrointestinal tract hemorrhage with no potential site having been identified by other investigations). Examinations were done using a Olympus video enteroscope (SIF-100) under general anesthesia in a one-day clinic. An upper tract examination was done first, directly followed by the lower tract investigation. RESULTS: The upper tract enteroscopy was successful in 53 patients (98%) and retrograde ileoscopy in 21 patients (39%). In 18 (38%) cases the technical failure resulted from the impossibility of intubating the ileocecal valve. A potential source of upper gastrointestinal bleeding was detected in 35% of patients with chronic iron-deficiency anemia and in 20% of those with unexplained gastrointestinal tract hemorrhage. The most common lesion in the small bowel was angiodysplasia (25%). The lower tract video push enteroscopy disclosed 11 lesions in patients with chronic anemia. However the lesions, including two ileocecal valve cancers, were mainly located in the colon and had been missed by previous colonoscopy. No case of ileal lesion was detected in this group of patients. In patients with unexplained gastrointestinal tract hemorrhage, three lesions were detected but only one of these was in the ileum. Associated colonic and jejunal lesions were observed in three patients (5.5%). Overall, the diagnostic yield of lower video push enteroscopy was less than 2%. CONCLUSION: This prospective study has shown that using an enteroscope as a colonoscope in the management of patients with gastrointestinal bleeding of unknown origin is of little help. It might actually be more appropriate to perform a second colonoscopy. This however remains controversial and a prospective study is needed to answer that question. [less ▲]

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See detailBronchial Eosinophilic Infiltration in Crohn's Disease in the Absence of Pulmonary Disease
Louis, Edouard ULg; Louis, Renaud ULg; Shute, J. et al

in Clinical & Experimental Allergy : Journal of the British Society for Allergy & Clinical Immunology (1999), 29(5), 660-6

BACKGROUND: Immunological and functional bronchopulmonary abnormalities may be present in up to two-thirds of patients with Crohn's disease. Having recently described a mild increase in methacholine ... [more ▼]

BACKGROUND: Immunological and functional bronchopulmonary abnormalities may be present in up to two-thirds of patients with Crohn's disease. Having recently described a mild increase in methacholine airways responsiveness in these patients, we investigated whether this physiological abnormality is associated with bronchial inflammation since it has previously been described in asthma. METHODS: Eighteen patients with Crohn's disease and 15 healthy controls matched for age, atopy and smoking habit, were studied. All the subjects underwent a bronchial methacholine challenge (1, 4 and 16 mg/mL) and a sputum induction by inhalation of hypertonic saline (NaCl 4.5%). The sputum samples were analysed for their cellular composition as well as for the levels of several mediators and proteins in the fluid phase, including eosinophil cationic protein (ECP), myeloperoxydase, albumin, alpha2-macroglobulin, interleukin-8 (IL-8), IgA and IL-8/immunoglobulin A complexes. RESULTS: When compared to control subjects, patients with Crohn's disease had significantly higher sputum eosinophil counts (14.5% [0-79.9%] vs 0.2% [0-2.3%]; P < 0. 001) and ECP levels (26.2 microg/L [4-124.2 microg/L] vs 9.8 microg/L [0-94.2 microg/L]; P < 0.05). However, patients with Crohn's disease had no sign of increased plasma exudation as reflected by sputum levels of albumin and alpha2-macroglobulin similar to those seen in control subjects. Furthermore the sputum levels of IL-8, IgA and IL-8/IgA complexes were not significantly different between the two groups. The magnitude of the fall in forced expiratory volume in 1 s after methacholine inhalation was significantly increased in Crohn's disease patients although it did not correlate with the extent of sputum eosinophilia or with the sputum ECP levels. CONCLUSIONS: Crohn's disease patients without any clinical respiratory involvement have airway eosinophilia without local increased plasma exudation. However, bronchial eosinophilia in Crohn's disease per se is not sufficient to induce clinically significant airway hyperresponsiveness, suggesting that other factors than bronchial eosinophilic infiltration are required for the clinical expression of an airway instability. [less ▲]

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See detailComment évaluer la sévérité d'un RGO et quels sont les objectifs thérapeutiques?
Louis, Edouard ULg; Marquis, P.; Nalet, B.

in Revue Médicale de Bruxelles (1999), 20(2), 114-5

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See detailLymphocytic colitis: a distinct clinical entity? A clinicopathological confrontation of lymphocytic and collagenous colitis.
Baert, F.; Wouters, K.; D'Haens, G. et al

in Gut (1999), 45(3), 375-81

BACKGROUND AND AIMS: It is not known whether lymphocytic colitis and collagenous colitis represent different clinical entities or constitute part of a spectrum of disease. METHODS: Detailed clinical ... [more ▼]

BACKGROUND AND AIMS: It is not known whether lymphocytic colitis and collagenous colitis represent different clinical entities or constitute part of a spectrum of disease. METHODS: Detailed clinical features and histological findings were compared in a large series of patients with confirmed lymphocytic and collagenous colitis. RESULTS: Histological diagnosis was confirmed in 96 patients with collagenous colitis and 80 with lymphocytic colitis. Twenty eight per cent of patients with collagenous colitis and 26% of patients with lymphocytic colitis had overlapping but less pronounced histological features. Both groups were equal in terms of age, use of aspirin and non-steroidal anti-inflammatory drugs, associated autoimmune conditions, arthritis, diarrhoea, and abdominal pain. The male:female ratio was 27:73 for collagenous colitis and 45:55 for lymphocytic colitis (p=0.013). Twenty five per cent of patients with collagenous colitis compared with 14% of patients with lymphocytic colitis were active smokers; only 8.3% of patients with collagenous colitis had stopped smoking compared with 23% of patients with lymphocytic colitis (p=0.013). Drug induced disease was suspected for ticlopidine (two collagenous colitis, four lymphocytic colitis) and flutamide (four lymphocytic colitis). Mean duration of symptoms before diagnosis was two months for lymphocytic colitis and four months for collagenous colitis. Overall prognosis was generally mild; 84% of patients with lymphocytic colitis and 74% of patients with collagenous colitis reported resolution or significant improvement (p=0.033). CONCLUSIONS: Collagenous and lymphocytic colitis are similar but not identical. Patients with lymphocytic colitis present somewhat earlier and are less likely to be active smokers. Symptoms are milder and more likely to disappear in lymphocytic colitis. Ticlopidine and flutamide should be added to the list of drugs inducing colitis. [less ▲]

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See detailSurveillance d'une maladie de Crohn en rémission de l'adulte
Belaiche, Jacques ULg; Louis, Edouard ULg

in Hépato-Gastro (1999), 6

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See detailMaladie de Crohn. Récidives post-opératoires. Conduite à tenir.
Belaiche, Jacques ULg; Louis, Edouard ULg

in Acta Endoscopica (1999), 29

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See detailTreatment of Inflammatory Bowel Disease with Azathioprine: How to Use It in 1999
Louis, Edouard ULg; Belaiche, Jacques ULg

in Acta Gastro-Enterologica Belgica (1999), 62(4, Oct-Dec), 437-9

Azathioprine and 6-mercaptopurine are effective drugs in the management of steroid dependent and chronic active inflammatory bowel diseases. They are also well tolerated on the long term. However, their ... [more ▼]

Azathioprine and 6-mercaptopurine are effective drugs in the management of steroid dependent and chronic active inflammatory bowel diseases. They are also well tolerated on the long term. However, their use is still hampered by some drawbacks including delay before efficacy, 20-35% of non responders, relapse at withdrawal of the drugs, possible bone marrow toxicity and other side effects. During the last few years, these drawbacks have been challenged by important studies showing that a better knowledge of the metabolism of these drugs may help to improve their use. [less ▲]

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See detailDecreased Corticosensitivity in Quiescent Crohn's Disease: An Ex Vivo Study Using Whole Blood Cell Cultures
Franchimont, Denis; Louis, Edouard ULg; Dupont, Pierre et al

in Digestive Diseases & Sciences (1999), 44(6), 1208-15

Corticosensitivity influences the degree and the duration of an inflammatory reaction by altering target cell responses to endogenous and/or exogenous glucocorticoids. Indeed, different clinical responses ... [more ▼]

Corticosensitivity influences the degree and the duration of an inflammatory reaction by altering target cell responses to endogenous and/or exogenous glucocorticoids. Indeed, different clinical responses to glucocorticoids have been observed among patients with Crohn's disease, suggesting different degrees of corticosensitivity in these subjects. The purpose of this study was to compare the corticosensitivity of patients with quiescent Crohn's disease to that of healthy subjects (HS). Nineteen patients with quiescent Crohn's disease and 14 HS were studied; all patients were steroid-free for at least six months; 7 of the 19 were corticosteroid-dependent (CSD) and treated with nonglucocorticoid immunosuppressants at the time of the study. Corticosensitivity was measured by the inhibition of LPS-induced cytokine secretion in whole blood cell cultures treated with increasing concentrations (10(-9) to 10(-6) M) of dexamethasone. Tumor-necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-1 beta (IL-1 beta) were measured using specific immunoassays. Crohn's disease patients had a markedly decreased dexamethasone-mediated inhibition of TNF-alpha (P < 0.01), IL-6 (P < 0.001), and IL-1 beta (P < 0.01) compared to healthy subjects, with a shift of the dexamethasone dose-response curve to the right. No significant differences in the basal and LPS-stimulated secretion of the three cytokines were observed between CSD and non-CSD patients, and both subgroups of patients had similar degrees of dexamethasone-mediated cytokine inhibition. We conclude that patients with Crohn's disease have a significant decrease in the corticosensitivity of their leukocytes. This may be related to a specific genetic/constitutional background and/or could be acquired, due to inflammation-related endocrine and/or immune factors. [less ▲]

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See detailCorticosensitivity in whole blood cell cultures in Crohn's disease and healthy subjects
Franchimont, Denis; Louis, Edouard ULg; Geenen, Vincent ULg et al

in Digestive Diseases & Sciences (1999), 44

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See detailClinical Pattern of Corticosteroid Dependent Crohn's Disease
Franchimont, D. P.; Louis, Edouard ULg; Croes, F. et al

in European Journal of Gastroenterology & Hepatology (1998), 10(10), 821-5

OBJECTIVES: Corticosteroid dependency in Crohn's disease (CD) is characterized by the need for chronic use of corticosteroids to maintain clinical remission. Several definitions have been used. Depending ... [more ▼]

OBJECTIVES: Corticosteroid dependency in Crohn's disease (CD) is characterized by the need for chronic use of corticosteroids to maintain clinical remission. Several definitions have been used. Depending on the definition, 10-30% of the patients are considered as corticosteroid dependent. The aim of the study was to define a clinical pattern of corticosteroid dependent CD patients. PATIENTS AND METHODS: Epidemiological and clinical characteristics were retrospectively compared between 20 corticosteroid dependent CD patients and 248 non-corticosteroid dependent CD patients by using univariate and multivariate analyses. Corticosteroid dependency was defined either by two successive relapses during the 2 months after discontinuing glucocorticoids (n=5) or by two successive relapses at dose tapering, after successful treatment of a flare-up by using glucocorticoids (n=15). RESULTS: Corticosteroid dependent CD patients were younger at diagnosis (P < 0.001), and were characterized by a higher frequency of colonic location (P< 0.05), but lower frequency of ileal location (P < 0.01), and higher ano-perineal location (P < 0.05). They were also more frequently smokers (P< 0.05) and users of contraceptive pills (P< 0.01). The inflammatory type of the disease was increased (P < 0.01), while the fibrostenotic type was decreased (P < 0.001) in corticosteroid dependent CD patients. By multivariate analysis, a smoking habit (P < 0.01), a colonic location (P < 0.05), a non-fibrostenotic type (P< 0.05) and a younger age at diagnosis (P< 0.05) were shown to be independently associated with corticosteroid dependency. CONCLUSIONS: This study suggests a clinical pattern associated with corticosteroid dependency. Whether this clinical pattern is simply associated with the dependency, or whether a primary decrease of corticosensitivity produces this clinical pattern, is not known. Further prospective studies will have to determine whether the presence of these clinical characteristics is predictive of corticosteroid dependency and whether this prediction will be useful for the management of this condition. [less ▲]

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See detailEffects of Dexamethasone on the Profile of Cytokine Secretion in Human Whole Blood Cell Cultures
Franchimont, Denis; Louis, Edouard ULg; Dewé, Walthère ULg et al

in Regulatory Peptides (1998), 73(1), 59-65

EXPERIMENTAL OBJECTIVES: The interaction between the endocrine and immune systems is a very intriguing area. Endogenous glucocorticoids, as end-effectors of the hypothalamo-pituitary-adrenal axis, inhibit ... [more ▼]

EXPERIMENTAL OBJECTIVES: The interaction between the endocrine and immune systems is a very intriguing area. Endogenous glucocorticoids, as end-effectors of the hypothalamo-pituitary-adrenal axis, inhibit the immune and inflammatory responses and are used as immunosuppressive drugs in many inflammatory, autoimmune and allergic diseases. The aims of this study were to investigate the effects of dexamethasone on the profile of cytokine secretion in whole blood cell cultures from healthy subjects and to analyse the gender-related sensitivity to dexamethasone on each cytokine secretion. RESULTS: There was a significant inhibition by dexamethasone (from 1 to 100 nM) on the secretion of monokines (IL-1beta, IL-6, IL-8 and TNF alpha) and lymphokines (IL-2, IL-4, IL-10 and IFN gamma), either after LPS or PHA stimulation (P < 0.01). Interleukin 4 and IL-10 were less inhibited than IFN gamma (P < 0.05 at 1 nM, P < 0.01 at 10 nM and P < 0.001 from 100 nM to 10 microM). No gender difference was observed in the rate of inhibition of the secretion of each cytokine. CONCLUSION: This study shows that the inhibition of cytokine secretion by dexamethasone is more marked on Th1-type cytokines than on Th2-type cytokines. These data support the idea that glucocorticoids may induce a shift from the Th1 to Th2 profile of cytokine secretion. [less ▲]

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