scholarly journals Studies on the Interleukin-10 Gene in Animal Models of Colitis

2001 ◽  
Vol 15 (8) ◽  
pp. 557-558
Author(s):  
Hugh J Freeman
Keyword(s):  
Inflammatory Bowel Disease ◽  
Animal Models ◽  
Bowel Disease ◽  
Inflammatory Process ◽  
Intestinal Inflammation ◽  
Therapeutic Potential ◽  
Interleukin 10 ◽  
Necrosis Factor Alpha ◽  
Inflammatory Bowel ◽  
Deficient Mice

Cytokines play a role in the inflammatory process in colitis and may have therapeutic potential. Interleukin-10 (IL-10) has both immunomodulatory and anti-inflammatory properties. IL-10-deficient mice develop intestinal inflammation with increased tissue levels of other cytokines, including tumour necrosis factor-alpha. In patients with inflammatory bowel disease, impaired IL-10 production by lamina propria T cells occurs and human recombinant IL-10 improves clinical parameters in inflammatory bowel disease (eg, Crohn's disease). There seem to be conflicting results in differing animal models, and the timing of administration of IL-10 relative to onset of colitis may be critical, possibly due to rapid clearance of IL-10. Interestingly, in IL-10 gene-deficient mice raised in germ-free conditions, the intestinal inflammatory changes normally observed in conventional nongerm-free conditions are not detected, suggesting a role for luminal bacteria in the pathogenesis of the inflammatory process.

scholarly journals Reducing Pain in Experimental Models of Intestinal Inflammation Affects the Immune Response

2021 ◽  
Author(s):  
Laura Golusda ◽  
Anja A Kühl ◽  
Britta Siegmund ◽  
Daniela Paclik
Keyword(s):  
Inflammatory Bowel Disease ◽  
Immune Response ◽  
Animal Models ◽  
Bowel Disease ◽  
Inflammatory Process ◽  
Intestinal Inflammation ◽  
Pain Medication ◽  
Experimental Models ◽  
Current Form ◽  
Inflammatory Bowel

Abstract The incidence of inflammatory bowel disease with its two main manifestations, colitis ulcerosa and Crohn’s disease, is rising globally year after year. There is still a tremendous need to study the underlying pathomechanisms and a well-established tool in order to better understand the disease are colitis models in rodents. Since the concept of the 3Rs was proposed by Russell and Burch, this would include pain medication in animal models of intestinal inflammation as a reduction of suffering. This review argues against pain medication because the administration of pain medication in its current form has an impact on the inflammatory process and the immune response, thus falsifying the results and the reproducibility and therefore leading to misconceptions.

Physiological Basis for Novel Drug Therapies Used to Treat the Inflammatory Bowel Diseases I. Immunology and therapeutic potential of antiadhesion molecule therapy in inflammatory bowel disease

2005 ◽  
Vol 288 (2) ◽  
pp. G169-G174 ◽  
Author(s):  
Gert Van Assche ◽  
Paul Rutgeerts
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Adhesion Molecules ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Therapeutic Potential ◽  
Physiological Basis ◽  
Inflammatory Bowel

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.

scholarly journals Considerations for Choosing Appropriate Animal Models to Study Inflammatory Bowel Disease

2016 ◽  
Vol 8 (7) ◽  
pp. 1
Author(s):  
Richard R. E. Uwiera ◽  
Trina C. Uwiera ◽  
Janelle A. Jiminez ◽  
G. Douglas Inglis
Keyword(s):  
Inflammatory Bowel Disease ◽  
Animal Model ◽  
Animal Models ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Disease Process ◽  
Careful Consideration ◽  
Complete Understanding ◽  
Advantages And Disadvantages ◽  
Inflammatory Bowel

<p>This article examines several animal models used to investigate mechanisms involved in the induction and progression of inflammatory bowel disease in people. The use of appropriate animal models to study intestinal inflammation requires careful consideration as each model has strengths and limitations for investigating disease, and no single model provides a complete understanding of the disease process. In as such, it compels researchers to carefully contemplate the advantages and disadvantages of each animal model, and to consider the process of choosing the best animal model(s) as an essential component of the experimental design.</p>

scholarly journals Probiotic Lactobacillus spp. Diminish Helicobacter hepaticus-Induced Inflammatory Bowel Disease in Interleukin-10-Deficient Mice

2005 ◽  
Vol 73 (2) ◽  
pp. 912-920 ◽  
Author(s):  
Jeremy A. Peña ◽  
Arlin B. Rogers ◽  
Zhongming Ge ◽  
Vivian Ng ◽  
Sandra Y. Li ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Real Time ◽  
Bowel Disease ◽  
Interleukin 10 ◽  
Helicobacter Hepaticus ◽  
Murine Colitis ◽  
Tnf Α ◽  
Inflammatory Bowel ◽  
Deficient Mice ◽  
Colitis Model

ABSTRACT Clinical and experimental evidence has demonstrated the potential role of probiotics in the prevention or treatment of inflammatory bowel disease. Probiotic clones with direct immunomodulatory activity may have anti-inflammatory effects in the intestine. We investigated the roles of tumor necrosis factor alpha (TNF-α)-inhibitory Lactobacillus clones with a pathogen-induced murine colitis model. Murine-derived probiotic lactobacilli were selected in vitro for their ability to inhibit TNF-α secretion by Helicobacter hepaticus-stimulated macrophages. Interleukin-10 (IL-10)-deficient mice were treated with probiotic Lactobacillus reuteri in combination with Lactobacillus paracasei and then challenged with H. hepaticus. Ten weeks postinoculation, the severity of typhlocolitis was assessed by histologic examination of the cecocolic region. Intestinal proinflammatory cytokine responses were evaluated by real-time quantitative reverse transcriptase PCR and immunoassays, and the quantities of intestinal H. hepaticus were evaluated by real-time PCR. Intestinal colonization by TNF-α-inhibitory lactobacilli reduced intestinal inflammation in H. hepaticus-challenged IL-10-deficient mice despite similar quantities of H. hepaticus in cocolonized animals. Proinflammatory colonic cytokine (TNF-α and IL-12) levels were lowered in Lactobacillus-treated animals. In this H. hepaticus-challenged IL-10-deficient murine colitis model, lactobacilli demonstrated probiotic effects by direct modulation of mucosal inflammatory responses.

Natural Colonization with Helicobacter species and the Development of Inflammatory Bowel Disease in Interleukin-10-deficient Mice

Helicobacter ◽  
2005 ◽  
Vol 10 (3) ◽  
pp. 223-230 ◽  
Author(s):  
Li Zhang ◽  
Stephen J. Danon ◽  
Martin Grehan ◽  
Vivian Chan ◽  
Adrian Lee ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Interleukin 10 ◽  
Inflammatory Bowel ◽  
Deficient Mice

scholarly journals The Impact of Farnesoid X Receptor Activation on Intestinal Permeability in Inflammatory Bowel Disease

2012 ◽  
Vol 26 (9) ◽  
pp. 631-637 ◽  
Author(s):  
Maja Stojancevic ◽  
Karmen Stankov ◽  
Momir Mikov
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Intestinal Tract ◽  
Intestinal Inflammation ◽  
Strong Support ◽  
Receptor Activation ◽  
Farnesoid X Receptor ◽  
Necrosis Factor Alpha ◽  
Inflammatory Bowel ◽  
The Impact

The most important function of the intestinal mucosa is to form a barrier that separates luminal contents from the intestine. Defects in the intestinal epithelial barrier have been observed in several intestinal disorders such as inflammatory bowel disease (IBD). Recent studies have identified a number of factors that contribute to development of IBD including environmental triggers, genetic factors, immunoregulatory defects and microbial exposure. The current review focuses on the influence of the farnesoid X receptor (FXR) on the inhibition of intestinal inflammation in patients with IBD. The development and investigation of FXR agonists provide strong support for the regulatory role of FXR in mucosal innate immunity. Activation of FXR in the intestinal tract decreases the production of proinflammatory cytokines such as interleukin (IL) 1-beta, IL-2, IL-6, tumour necrosis factor-alpha and interferon-gamma, thus contributing to a reduction in inflammation and epithelial permeability. In addition, intestinal FXR activation induces the transcription of multiple genes involved in enteroprotection and the prevention of bacterial translocation in the intestinal tract. These data suggest that FXR agonists are potential candidates for exploration as a novel therapeutic strategy for IBD in humans.

scholarly journals GPR4 Deficiency Alleviates Intestinal Inflammation in a Mouse Model of Inflammatory Bowel Disease

2016 ◽  
Author(s):  
Edward J. Sanderlin ◽  
Nancy R. Leffler ◽  
Kvin Lertpiriyapong ◽  
Qi Cai ◽  
Heng Hong ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Mouse Model ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Vascular Endothelial Cells ◽  
Leukocyte Adhesion ◽  
Lymphoid Follicle ◽  
Wild Type ◽  
Inflammatory Bowel ◽  
Deficient Mice

AbstractGPR4 is a proton-sensing G protein-coupled receptor that can be activated by extracellular acidosis. It has recently been demonstrated that activation of GPR4 by acidosis increases the expression of numerous inflammatory and stress response genes in vascular endothelial cells (ECs) and also augments EC-leukocyte adhesion. Inhibition of GPR4 by siRNA or small molecule inhibitors reduces endothelial cell inflammation. As acidotic tissue microenvironments exist in many types of inflammatory disorders, including inflammatory bowel disease (IBD), we examined the role of GPR4 in IBD using a dextran sulfate sodium (DSS)-induced colitis mouse model. We observed that GPR4 mRNA expression was increased in mouse and human IBD tissues when compared to control intestinal tissues. To determine the function of GPR4 in IBD, wild-type and GPR4-deficient mice were treated with 3% DSS for 7 days to induce acute colitis. Our results showed that the severity of colitis was decreased in GPR4-deficient DSS-treated mice in comparison to wild-type DSS-treated mice. Clinical parameters, macroscopic disease indicators, and histopathological features were less severe in the DSS-treated GPR4-deficient mice than the DSS-treated wild-type mice. Inflammatory gene expression, leukocyte infiltration, and isolated lymphoid follicle (ILF) formation were reduced in intestinal tissues of DSS-treated GPR4-null mice. Collectively, our results suggest GPR4 provides a pro-inflammatory role in IBD as the absence of GPR4 ameliorates intestinal inflammation in the acute DSS-induced IBD mouse model.

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