scholarly journals The Multifaceted Role of the Inflammasome in Inflammatory Bowel Diseases

2011 ◽  
Vol 11 ◽  
pp. 1536-1547 ◽  
Author(s):  
Donata Lissner ◽  
Britta Siegmund

Inflammasomes are intracellular multiprotein complexes that coordinate the maturation of interleukin (IL)-1β and IL-18 in response to pathogens and metabolic danger. Both cytokines have been linked to intestinal inflammation. However, recently evolving concepts ascribe a major role to the inflammasome in maintaining intestinal homeostasis. This review recapitulates its position in the development of inflammatory bowel disease, thereby outlining a model in which hypo- as well as hyperfunctionality can lead to an imbalance of the system, depending on the specific cell population affected. In the epithelium, the inflammasome is essential for regulation of permeability and epithelial regeneration through sensing of commensal microbes, while excessive inflammasome activation within the lamina propria contributes to severe intestinal inflammation.

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 772-772
Author(s):  
P. Kulakova ◽  
G. Lukina ◽  
E. Alexandrova ◽  
A. Novikov ◽  
A. Klimets ◽  
...  

Background:Аnkylosing spondylitis (AS) and inflammatory bowel diseases (IBD) have many common features. Approximately one in two patients with axial spondyloarthritis have subclinical (histologically confirmed) inflammation of the intestine, and 5-10% of subclinical inflammation turns into Crohn’s disease (CD) or Ulcerative colitis (UC) [1]. Colonoscopy is usually used to diagnose IBD, but this procedure is invasive. Laboratory biomarkers, as fecal calprotectin (FC) and serum calprotectin (SC) can used to diagnosis of IBD. But there is no consensus regarding SC clinical utility. SC is exposed to proteolytic enzymes, but its level also increases with inflammation in the intestine and is associated with a higher disease activity [2]. SC levels positively correlate with CRP, ESR, disease activity in AS, but not as obvious as with FC [3,4].Objectives:The aim of this study was to evaluate the possibility of using SC in the diagnosis of IBD in patients with AS.Methods:In the analysis were included 50 patients with AS, fulfilling the modified New York criteria, among them man -36 (72%), woman -14 (28%), mean age of patients was 42.5 ±9.9, mean disease duration – 13.4±8.7 years. All patients were examined with ESR, CRP, FC (range: 100-1800 µg /g), esophagogastroduodenoscopy, colonoscopy and quantitative analysis of the SC level using ELISA (BUHLMANN MRP8/14 ELISA, range: 0.4-3.9 µg /ml).Results:All patients had a high disease activity, mean BASDAI was 5.3 ± 1.8, mean ASDAS CRP 3.7 ± 1.01, mean ASDAS ESR 3.6 ± 1.01. 80 % patients had high FC level (more than 100 µg / g), while only 18% patients had an increase of SC level. IBD were diagnosed in 11 cases: 6 patients (12 %) with CD and 5 patients (10 %) - UC, in the remaining cases (78%) was no intestinal pathology. Only 2 patients with IBD had a high SC level. SC level was more correlated with ESR (r=0.5) and CRP (r=0.5) (p <0.05) levels, than with FC level (r=0.4) (p <0.05).Conclusion:The results showed that there is currently insufficient data to assess the possibility of using SC in the diagnosis of IBD in patients with AS. There is a significant association between the SC, CRP and ESR, but not fecal calprotectin. Potentially SC may be more representative of systemic inflammation than an intestinal inflammation.References:[1]Klingberg, E., Strid, H., Stahl, A.et al. A longitudinal study of fecal calprotectin and the development of inflammatory bowel disease in ankylosing spondylitis. A longitudinal study of fecal calprotectin and the development of inflammatory bowel disease in ankylosing spondylitis. Arthritis Res Ther 2017. 19(1):21[2]Kalla R, Kennedy NA, Ventham NT, Boyapati RK, Adams AT, Nimmo ER, Visconti MR, Drummond H, Ho GT, Pattenden RJ, Wilson DC, Satsangi J. Serum Calprotectin: A Novel Diagnostic and Prognostic Marker in Inflammatory Bowel Diseases. Am J Gastroenterol. 2016 Dec;111(12):1796-1805[3]Hu H, Du F, Zhang S, Zhang W. Serum calprotectin correlates with risk and disease severity of ankylosing spondylitis and its change during first month might predict favorable response to treatment. Mod Rheumatol. 2019 Sep;29(5):836-842.[4]Azramezani Kopi T, Shahrokh S, Mirzaei S, Asadzadeh Aghdaei H, Amini Kadijani A. The role of serum calprotectin as a novel biomarker in inflammatory bowel diseases: a review study. Gastroenterol Hepatol Bed Bench. 2019;12(3):183-189.Disclosure of Interests:None declared.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
A. Angeletti ◽  
S. Arrigo ◽  
A. Madeo ◽  
M. Molteni ◽  
E. Vietti ◽  
...  

Abstract Background Inflammatory bowel diseases are characterized by chronic inflammation of the gastrointestinal tract. In particular, Crohn disease and ulcerative colitis represent the two most common types of clinical manifestations. Extraintestinal manifestations of inflammatory bowel diseases represent a common complications, probably reflecting the systemic inflammation. Renal involvement is reported in 4–23% of cases. However, available data are limited to few case series and retrospective analysis, therefore the real impact of renal involvement is not well defined. Case presentation We report the case of a 10-years old male affected by very early onset unclassified-Inflammatory bowel diseases since he was 1-year old, presenting with a flare of inflammatory bowel diseases associated with acute kidney injury due to granulomatous interstitial nephritis. Of interest, at 7-year-old, he was treated for IgA nephropathy. To our knowledge, no previous reports have described a relapse of renal manifestation in inflammatory bowel diseases, characterized by two different clinical and histological phenotypes. Conclusions The link between the onset of kidney injuries with flares of intestinal inflammation suggest that nephritis maybe considered an extra-intestinal manifestation correlated with active inflammatory bowel disease. However, if granulomatous interstitial nephritis represents a cell-mediated hypersensitivity reaction than a true extraintestinal manifestation of inflammatory bowel diseases is still not clarified. We suggest as these renal manifestations here described may be interpreted as extraintestinal disorder and also considered as systemic signal of under treatment of the intestinal disease.


2021 ◽  
Vol 75 (1) ◽  
pp. 20-28
Author(s):  
Vladimír Teplan ◽  
Milan Lukáš

The incidence and prevalence of overweight and obesity has dramatically increased in the last decades and is generally considered to be global pandemics. The incidence of inflammatory bowel disease (IBD) is rising parallel with overweight and obesity. Contrary to a conventional believe, about 15–40% patients with IBD are obese, which can contribute to the development and course of IBD, especially in Crohn’s disease. Although the findings of some cohort studies are still conflicting, recent results indicate a special role of visceral adipose tissue and particularly mesenteric adipose tissue known as creeping fat, leading to intestinal inflammation. The involvement of altered adipocyte function and deregulated production of adipokines such as leptin and adiponectin has been suggested in the pathogenesis of IBD. The emerging role of Western diet and microbiota can also open new possibilities in IBD management. The effect of obesity on the IBD-related therapy remains to be studied. The finding that obesity results in suboptimal response to the therapy, potentially promoting rapid clearance of biologic agents and thus leading to their low concentrations, has a great importance. Obesity also makes IBD colorectal surgery technically challenging and might increase a risk of perioperative complications.


2008 ◽  
Vol 105 (46) ◽  
pp. 17931-17936 ◽  
Author(s):  
Danyvid Olivares-Villagómez ◽  
Yanice V. Mendez-Fernandez ◽  
Vrajesh V. Parekh ◽  
Saif Lalani ◽  
Tiffaney L. Vincent ◽  
...  

Intestinal intraepithelial lymphocytes (IEL) bear a partially activated phenotype that permits them to rapidly respond to antigenic insults. However, this phenotype also implies that IEL must be highly controlled to prevent misdirected immune reactions. It has been suggested that IEL are regulated through the interaction of the CD8αα homodimer with the thymus leukemia (TL) antigen expressed by intestinal epithelial cells. We have generated and characterized mice genetically-deficient in TL expression. Our findings show that TL expression has a critical role in maintaining IEL effector functions. Also, TL deficiency accelerated colitis in a genetic model of inflammatory bowel disease. These findings reveal an important regulatory role of TL in controlling IEL function and intestinal inflammation.


Rheumatology ◽  
2020 ◽  
Vol 59 (11) ◽  
pp. 3275-3283 ◽  
Author(s):  
Anastasia Dupré ◽  
Michael Collins ◽  
Gaétane Nocturne ◽  
Franck Carbonnel ◽  
Xavier Mariette ◽  
...  

Abstract Objective Vedolizumab (VDZ) has been incriminated in the occurrence of articular manifestations in patients with inflammatory bowel diseases (IBDs). The aim of this study was to describe musculoskeletal manifestations occurring in IBD patients treated by VDZ and to identify risk factors. Methods In this retrospective monocentric study, we included all consecutive patients treated by VDZ for IBD in our hospital. Incident musculoskeletal manifestations occurring during VDZ treatment were analysed and characteristics of patients with and without articular inflammatory manifestations were compared. Results Between 2013 and 2017, 112 patients were treated with VDZ for IBD: ulcerative colitis (n = 59), Crohn’s disease (n = 49) and undetermined colitis (n = 4). Four patients (3.6%) had a history of SpA, whereas 13 (11.6%) had a history of peripheral arthralgia. Some 102 (91.1%) patients had previously received anti-TNF. After a mean (S.d.) follow-up of 11.4 (8.6) months, 32 (28.6%) patients presented 35 musculoskeletal manifestations, of which 18 were mechanical and 17 inflammatory. Among the latter, 11 had axial or peripheral SpA, 5 had early reversible arthralgia and 1 had chondrocalcinosis (n = 1). Among the 11 SpA patients, only 3 (2.6%) had inactive IBD and may be considered as paradoxical SpA. The only factor associated with occurrence of inflammatory manifestations was history of inflammatory articular manifestation [7/16 (43.8%) vs 10/80 (12.5%), P = 0.007]. Conclusion Musculoskeletal manifestations occurred in almost 30% of IBD patients treated with VDZ, but only half of them were inflammatory. Since most of the patients previously received anti-TNF, occurrence of inflammatory articular manifestations might rather be linked to anti-TNF discontinuation than to VDZ itself.


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