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

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.

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

Canadian Journal of Gastroenterology ◽

10.1155/2001/303729 ◽

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.

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Considerations for Choosing Appropriate Animal Models to Study Inflammatory Bowel Disease

Journal of Agricultural Science ◽

10.5539/jas.v8n7p1 ◽

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>

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Review article: How relevant to human inflammatory bowel disease are current animal models of intestinal inflammation?

Alimentary Pharmacology & Therapeutics ◽

10.1111/j.1365-2036.1997.tb00813.x ◽

2010 ◽

Vol 11 ◽

pp. 89-97 ◽

Cited By ~ 22

Author(s):

R. B. SARTOR

Keyword(s):

Inflammatory Bowel Disease ◽

Animal Models ◽

Bowel Disease ◽

Intestinal Inflammation ◽

Review Article ◽

Human Inflammatory Bowel Disease ◽

Inflammatory Bowel

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Recent Trends in Pharmacological Activity of Alkaloids in Animal Colitis: Potential Use for Inflammatory Bowel Disease

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2017/8528210 ◽

2017 ◽

Vol 2017 ◽

pp. 1-24 ◽

Cited By ~ 13

Author(s):

Ana Cristina Alves de Almeida ◽

Felipe Meira de-Faria ◽

Ricardo José Dunder ◽

Luis Paulo Bognoni Manzo ◽

Alba Regina Monteiro Souza-Brito ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Pharmacological Activity ◽

Bowel Disease ◽

Intestinal Inflammation ◽

Biological Activities ◽

Plant Secondary Metabolites ◽

Experimental Models ◽

Free Radical Scavengers ◽

Recent Trends ◽

Inflammatory Bowel

Inflammatory bowel disease (IBD) is a chronic and disrupted inflammation of the gastrointestinal tract. IBD have two main conditions, Crohn’s disease and ulcerative colitis, and have been extensively investigated in recent years. Antibiotics derived from salicylates, steroids, immunosuppressors, and anti-TNF therapy are part of the therapeutic arsenal for IBD. However, very often patients stop responding to treatments over the time. In this context, searching for alternative agents is crucial for IBD clinical management. Natural products derived from medicinal plants are an interesting therapeutic alternative, since several studies have proven effective treatments in animal models of intestinal inflammation. Several naturally occurring compounds are potent antioxidants, both as free radical scavengers and as modulators of antioxidant enzymes expression and activity. A number of natural compounds have also been proved to inhibit the release of proinflammatory cytokines, decreasing the activation of nuclear factorκB (NF-κB), which is important to the inflammatory response in IBD. The alkaloids are substances of a very diverse class of plant secondary metabolites; an extensive list of biological activities has been attributed to alkaloids, such as being anticholinergic, antitumor, diuretic, antiviral, antihypertensive, antiulcer, analgesic, and anti-inflammatory. In the present work, studies on the pharmacological activity of alkaloids in experimental models of IBD were reviewed.

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Animal models of intestinal inflammation: new insights into the molecular pathogenesis and immunotherapy of inflammatory bowel disease

International Journal of Colorectal Disease ◽

10.1007/s003840000227 ◽

2000 ◽

Vol 15 (3) ◽

pp. 144-160 ◽

Cited By ~ 101

Author(s):

Stefan Wirtz ◽

M. F. Neurath

Keyword(s):

Inflammatory Bowel Disease ◽

Animal Models ◽

Bowel Disease ◽

Intestinal Inflammation ◽

Molecular Pathogenesis ◽

Inflammatory Bowel

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An Update of Research Animal Models of Inflammatory Bowel Disease

The Scientific World JOURNAL ◽

10.1155/2021/7479540 ◽

2021 ◽

Vol 2021 ◽

pp. 1-12

Author(s):

Zineb Baydi ◽

Youness Limami ◽

Loubna Khalki ◽

Nabil Zaid ◽

Abdallah Naya ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Animal Models ◽

Bowel Disease ◽

Intestinal Inflammation ◽

Therapeutic Strategies ◽

Murine Models ◽

Immune System Dysfunction ◽

Inflammatory Bowel ◽

Underlying Mechanisms ◽

And Shifts

Inflammatory bowel disease (IBD) is a group of chronic disorders that includes two main disease forms, Crohn’s disease, and ulcerative colitis. The understanding of the intestinal inflammation occurring in IBD has been immeasurably advanced by the development of the now numerous murine models of intestinal inflammation. The usefulness of this research tool in IBD arises from a convergence of underlying genetic susceptibility, immune system dysfunction, environmental factors, and shifts in gut microbiota. Due to the multifactorial feature of these diseases, different animal models have been used to investigate the underlying mechanisms and develop potential therapeutic strategies. The results of preclinical efficacy studies often inform the progression of therapeutic strategies. This review describes the distinct feature and limitations of each murine IBD model and discusses the previous and current lessons from the IBD models.

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Food Additive Guar Gum Aggravates Colonic Inflammation in Experimental Models of Inflammatory Bowel Disease

Current Developments in Nutrition ◽

10.1093/cdn/nzab061_026 ◽

2021 ◽

Vol 5 (Supplement_2) ◽

pp. 1142-1142

Author(s):

Divek VT Nair ◽

Devendra Paudel ◽

Divya Prakash ◽

Vishal Singh

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Guar Gum ◽

Intestinal Inflammation ◽

Experimental Models ◽

Colonic Inflammation ◽

Epithelial Injury ◽

Amyloid A ◽

Inflammatory Bowel ◽

The Impact

Abstract Objectives Guar gum, a soluble fiber, is commonly used as a thickener, stabilizer, and source of fiber in processed foods. The food industry has been encouraged to fortify foods with refined guar gum due to its numerous beneficial effects on the human gut and metabolic health. However, we have limited knowledge on whether processed guar gum holds the same physiological effects as its naturally occurring counterpart. In this study, we examined the impact of refined guar gum on intestinal inflammation. Methods We employed three different experimental models of inflammatory bowel disease (IBD)—(1) immune hyperactivity [IL-10 receptor (IL-10R) neutralization], (2) epithelial injury [dextran sulfate sodium (DSS)], and 3) infection [Citrobacter rodentium (CR)]- mediated inflammation—to elucidate the effect of refined guar gum on IBD comprehensively. The colitis development was examined by serological, histological, and immunological parameters. Results Wild-type (WT, C57BL/6) mice receiving guar gum (7.5% w/w) containing diet (GuD) along with α-IL-10R displayed severe colonic inflammation—as characterized by an enlarged spleen, thickening of the colon, and elevated systemic [serum amyloid A (SAA), lipocalin 2 (Lcn2) and keratinocyte-derived chemokine (KC)] and colonic [Lcn2 and interleukin (IL)-1β] markers of inflammation—when compared to mice fed control (cellulose) diet. Histological examination of colonic sections displayed distorted and elongated crypt structure and reduced goblet cells. Inline, GuD-fed mice maintained on DSS (1.4% w/v) for seven days exhibited relatively worsened colitis compared to the control diet-fed group. Specifically, GuD-fed mice showed a more abrupt loss in body weight, diarrhea, rectal bleeding, shortening of colon length, and heightened proinflammatory cytokines, including KC, SAA, and Lcn2. In contrast to what we observed with immune hyperactivation and epithelial injury models, GuD did not exacerbate the CR-induced infectious colitis; however, no sign of protection was evident in the GuD-fed group. Conclusions This study collectively demonstrates that refined guar gum may heighten the intestinal inflammation in patients with IBD. Funding Sources This work is supported by a Career Development Award from the Crohn's & Colitis Foundation.

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