scholarly journals Recent Advances: The Imbalance of Cytokines in the Pathogenesis of Inflammatory Bowel Disease

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Qingdong Guan ◽  
Jiguo Zhang

Cytokines play an important role in the immunopathogenesis of inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, where they drive and regulate multiple aspects of intestinal inflammation. The imbalance between proinflammatory and anti-inflammatory cytokines that occurs in IBD results in disease progression and tissue damage and limits the resolution of inflammation. Targeting cytokines have been novel strategies in the treatment of IBD. Recent studies show the beneficial effects of anticytokine treatments to IBD patients, and multiple novel cytokines are found to be involved in the pathogenesis of IBD. In this review, we will discuss the recent advances of novel biologics in clinics and clinical trials, and novel proinflammatory and anti-inflammatory cytokines found in IBD with focusing on IL-12 family and IL-1 family members as well as their relevance to the potential therapy of IBD.

Marine Drugs ◽  
2021 ◽  
Vol 19 (6) ◽  
pp. 312
Author(s):  
Maria G. Daskalaki ◽  
Konstantinos Axarlis ◽  
Tone Aspevik ◽  
Michail Orfanakis ◽  
Ourania Kolliniati ◽  
...  

Inflammatory bowel disease is characterized by extensive intestinal inflammation, and therapies against the disease target suppression of the inflammatory cascade. Nutrition has been closely linked to the development and suppression of inflammatory bowel disease, which to a large extent is attributed to the complex immunomodulatory properties of nutrients. Diets containing fish have been suggested to promote health and suppress inflammatory diseases. Even though most of the health-promoting properties of fish-derived nutrients are attributed to fish oil, the potential health-promoting properties of fish protein have not been investigated. Fish sidestreams contain large amounts of proteins, currently unexploited, with potential anti-inflammatory properties, and may possess additional benefits through bioactive peptides and free amino acids. In this project, we utilized fish protein hydrolysates, based on mackerel and salmon heads and backbones, as well as flounder skin collagen. Mice fed with a diet supplemented with different fish sidestream-derived protein hydrolysates (5% w/w) were exposed to the model of DSS-induced colitis. The results show that dietary supplements containing protein hydrolysates from salmon heads suppressed chemically-induced colitis development as determined by colon length and pro-inflammatory cytokine production. To evaluate colitis severity, we measured the expression of different pro-inflammatory cytokines and chemokines and found that the same supplement suppressed the pro-inflammatory cytokines IL-6 and TNFα and the chemokines Cxcl1 and Ccl3. We also assessed the levels of the anti-inflammatory cytokines IL-10 and Tgfb and found that selected protein hydrolysates induced their expression. Our findings demonstrate that protein hydrolysates derived from fish sidestreams possess anti-inflammatory properties in the model of DSS-induced colitis, providing a novel underexplored source of health-promoting dietary supplements.


2015 ◽  
Vol 10 (4) ◽  
pp. 860
Author(s):  
Irfan Ahmad Rather ◽  
Vivek K. Bajpai ◽  
Nam Gyeong-Jun

<p>Animal model of intestinal inflammation is of paramount significance that aids in discerning the pathologies underlying ulcerative colitis and Crohn’s disease, the two clinical presentations of inflammatory bowel disease. The 2,4,6-trinitrobenzene sulfonic acid (TNBS) colitis model represents one such intestinal inflammation-prototype that is generated in susceptible strains of mice through intra-rectal instillation of compound TNBS. In this paper, we demonstrate the experimental induction of TNBS-mediated colitis in a susceptible strain of ICR mice. This can be done by the following steps: a) acclimation, b) induction and c) observation. TNBS-mouse model provides the information in shortest possible time and simultaneously represents a cost effective and highly reproducible model method of studying the pathogenesis of inflammatory bowel disease.</p><p><strong>Video Clips</strong></p><p><a href="https://youtube.com/v/6MsuIGzH3uA">Acclimation and induction of TNBS</a>:          4.5 min</p><p><a href="https://youtube.com/v/ya66SNwoVag">Observation and drug administration</a>:      1.5 min</p>


2005 ◽  
Vol 288 (2) ◽  
pp. G169-G174 ◽  
Author(s):  
Gert Van Assche ◽  
Paul Rutgeerts

Adhesion molecules regulate the influx of leukocytes in normal and inflamed gut. They are also involved in local lymphocyte stimulation and antigen presentation within the intestinal mucosa. In intestinal inflammation, many adhesion molecules are upregulated, but α4-integrins most likely hold a key position in directing leukocytes into the inflamed bowel wall. Therapeutic compounds directed against trafficking of leukocytes have been designed and are being developed as a novel class of drugs in the treatment of Crohn's disease and ulcerative colitis. This review deals with the immunological aspects of leukocyte trafficking focused on gut homing of T cells. Second, the changes in adhesion molecules and T cell trafficking during intestinal inflammation are discussed. Finally, we review the clinical data that have been gathered with respect to the therapeutic potential and the safety of antiadhesion molecule treatment. Antegren, or natalizumab, a humanized anti-α4 integrin IgG4 antibody, has been most extensively evaluated and may be close to registration. A more specific humanized α4β7-integrin MLN-02 has shown preliminary clinical efficacy in ulcerative colitis, and both antergren and MLN-02 appear to be very safe. Trials with the anti-ICAM-1 antisense oligonucleotide ISIS-2302 in steroid refractory Crohn's disease have provided conflicting efficacy data. In the near future, some of these novel biological agents may prove valuable therapeutic tools in the management of refractory inflammatory bowel disease, although it is too early to define the patient population that will benefit most from these agents.


Medicina ◽  
2008 ◽  
Vol 44 (1) ◽  
pp. 27 ◽  
Author(s):  
Jurgita Šventoraitytė ◽  
Aida Žvirblienė ◽  
Gediminas Kiudelis ◽  
Rimantas Žalinkevičius ◽  
Aurelija Žvirblienė ◽  
...  

Objective. Perturbed immune homeostasis elicited by misbalanced production of proinflammatory and anti-inflammatory cytokines is characteristic of inflammatory bowel disease. The aim of this study was to evaluate cytokine profile in patients with different forms of inflammatory bowel disease – ulcerative colitis and Crohn’s disease – during clinical remission phase. Material and methods. Production of proinflammatory Th1 cytokines (tumor necrosis factoralpha (TNF-a), interferon-gamma (IFN-g)) and anti-inflammatory Th2 cytokines (interleukin- 10 (IL-10) and interleukin-13 (IL-13)) was analyzed in peripheral blood mononuclear cells of patients with inflammatory bowel disease (9 with ulcerative colitis and 9 with Crohn’s disease) and control subjects (n=11) by enzyme-linked immunosorbent assay (two-site ELISA). Results. The results of the study revealed that the level of TNF-a after stimulation with phytohemagglutinin in patients with Crohn’s disease was significantly higher in comparison to both patients with ulcerative colitis and controls (P<0.001 and P<0.01, respectively). The secretion of IFN-g both in patients with Crohn’s disease and ulcerative colitis was lower than that in controls (P=0.05 and P<0.01, respectively), but it normalized after stimulation with phytohemagglutinin. The levels of IL-10 and IL-13 were significantly (P<0.01) higher in patients with Crohn’s disease than in patients with ulcerative colitis and control group before and after stimulation with phytohemagglutinin. Conclusions. The results of our study provide evidence that in patients with inflammatory bowel disease, the imbalance between production of proinflammatory Th1 and anti-inflammatory Th2 cytokines persists even during remission of the disease, and disturbances of immune homeostasis are significantly more expressed in patients with Crohn’s disease than in patients with ulcerative colitis.


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Carlijn R. Lamers ◽  
Nicole M. de Roos ◽  
Ben J. M. Witteman

Abstract Background Diet may play a role in disease status in patients with inflammatory bowel disease. We tested whether the inflammatory potential of diet, based on a summation of pro- and anti-inflammatory nutrients, is associated with disease activity in patients with Crohn’s disease and ulcerative colitis. Methods Participants completed a disease activity questionnaire (short Crohn’s Disease Activity (sCDAI) or Patient Simple Clinical Colitis Activity Index (P-SCCAI)) and a Food Frequency Questionnaire (FFQ). FFQ data were used to calculate the Dietary Inflammatory Index (DII) which enables categorization of individuals’ diets according to their inflammatory potential on a continuum from pro- to anti-inflammatory. Associations with disease activity were investigated by multiple linear regression. Results The analysis included 329 participants; 168 with Crohn’s disease (median sCDAI score 93 [IQR 47–156]), and 161 with ulcerative colitis (median P-SCCAI score 1 [IQR 1–3]). Mean DII was 0.71 ± 1.33, suggesting a slightly pro-inflammatory diet. In Crohn’s disease, the DII was positively associated with disease activity, even after adjustment for confounders (p = 0.008). The mean DII was significantly different between participants in remission and with mild and moderately active disease (0.64, 0.97 and 1.52 respectively, p = 0.027). In ulcerative colitis, the association was not significant. Conclusions Disease activity was higher in IBD participants with a more pro-inflammatory diet with statistical significance in Crohn’s disease. Although the direction of causality is not clear, this association strengthens the role for diet in medical treatment, which should be tested in an intervention study.


2020 ◽  
Vol 10 (23) ◽  
pp. 8465
Author(s):  
João Rocha ◽  
Raquel Leandro ◽  
Rosa Direito ◽  
Margarida Gonçalves ◽  
Maria Paula Duarte ◽  
...  

Summer Savory (Satureja hortensis L.) is a plant traditionally used as a food spice in the Mediterranean region. Surprisingly, not much is known about the health beneficial effects of its phenolic-rich extracts. The majority of publications have always focused on the properties of their essential oil. One of the main phenolic compounds of Summer Savory is rosmarinic acid, which has demonstrated anti-inflammatory outcomes in several animal models of inflammatory-mediated diseases. Inflammatory Bowel Disease (IBD) is a chronic inflammatory disease, in addition to Ulcerative Colitis and Crohn’s Disease, frequently related with increased morbidity and even mortality due to the complications associated, including colorectal cancer. Our work has shown, to our knowledge, for the first time, that administration of a phenolic extract of Summer Savory in a mouse model of Ulcerative Colitis led to the reduction of several markers for intestinal injury, including reduction of inducible nitric oxide synthase (iNOS) and Cyclooxygenase-2 (COX-2 or prostaglandin-endoperoxide synthase) expression, two well-known mediators of tissue inflammation and progression to cancer and led also to a reduction of the mortality. Given the chemical constitution found in the extract and the preclinical evidence of a beneficial effect of polyphenols in inflammatory processes, an opportunity arises for pharmacological modulation of pathways relevant for IBD and progression to cancer with phenolic-rich extracts.


2001 ◽  
Vol 120 (5) ◽  
pp. A184-A184
Author(s):  
K INA ◽  
Y KUNO ◽  
T MATSUURA ◽  
K KYOKANE ◽  
A IMADA ◽  
...  

PPAR Research ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Vito Annese ◽  
Francesca Rogai ◽  
Alessia Settesoldi ◽  
Siro Bagnoli

Peroxisome proliferator-activated receptor gamma (PPARγ) is member of a family of nuclear receptors that interacts with nuclear proteins acting as coactivators and corepressors. The colon is a major tissue which expresses PPARγin epithelial cells and, to a lesser degree, in macrophages and lymphocytes and plays a role in the regulation of intestinal inflammation. Indeed, both natural and synthetic PPARγligands have beneficial effects in different models of experimental colitis, with possible implication in the therapy of inflammatory bowel disease (IBD). This paper will specifically focus on potential role of PPARγin the predisposition and physiopathology of IBD and will analyze its possible role in medical therapy.


2015 ◽  
Vol 2015 ◽  
pp. 1-14 ◽  
Author(s):  
Francesca Algieri ◽  
Alba Rodriguez-Nogales ◽  
M. Elena Rodriguez-Cabezas ◽  
Severiano Risco ◽  
M. Angeles Ocete ◽  
...  

Crohn’s disease and ulcerative colitis are the two most common categories of inflammatory bowel disease (IBD), which are characterized by chronic inflammation of the intestine that comprises the patients’ life quality and requires sustained pharmacological and surgical treatments. Since their aetiology is not completely understood, nonfully efficient drugs have been developed and those that show effectiveness are not devoid of quite important adverse effects that impair their long-term use. Therefore, many patients try with some botanical drugs, which are safe and efficient after many years of use. However, it is necessary to properly evaluate these therapies to consider a new strategy for human IBD. In this report we have reviewed the main botanical drugs that have been assessed in clinical trials in human IBD and the mechanisms and the active compounds proposed for their beneficial effects.


Nutrients ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 1019 ◽  
Author(s):  
Jane Fletcher ◽  
Sheldon C. Cooper ◽  
Subrata Ghosh ◽  
Martin Hewison

Vitamin D has been linked to human health benefits that extend far beyond its established actions on calcium homeostasis and bone metabolism. One of the most well studied facets of extra-skeletal vitamin D is its activity as an immuno-modulator, in particular its potent anti-inflammatory effects. As a consequence, vitamin D deficiency has been associated with inflammatory diseases including inflammatory bowel disease (IBD). Low serum levels of the major circulating form of vitamin D, 25-hydroxyvitamin D (25-OH-D) are significantly more prevalent in patients with IBD, particularly in the winter and spring months when UV-induced synthesis of vitamin D is lower. Dietary malabsorption of vitamin D may also contribute to low serum 25(OH)D in IBD. The benefits of supplementation with vitamin D for IBD patients are still unclear, and improved vitamin D status may help to prevent the onset of IBD as well as ameliorating disease severity. Beneficial effects of vitamin D in IBD are supported by pre-clinical studies, notably with mouse models, where the active form of vitamin D, 1,25-dihydroxyvitamin D (1,25-(OH)2D) has been shown to regulate gastrointestinal microbiota function, and promote anti-inflammatory, tolerogenic immune responses. The current narrative review aims to summarise the different strands of data linking vitamin D and IBD, whilst also outlining the possible beneficial effects of vitamin D supplementation in managing IBD in humans.


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