Chemically induced mouse models of intestinal inflammation

Inciting Intestinal Inflammation

The ability to induce intestinal inflammation is crucial for studying complex diseases such as inflammatory bowel disease (IBD). However, the induction and progression of intestinal inflammation is complex and multifactorial—dependent on characteristics of both the host and environment, such as the age, genetic predisposition, and microbiome of the animal model being used.

Fortunately, you have several options for generating chemically induced mouse models of intestinal inflammation. Chemical agents are often considered the best methods to study acute and chronic immune responses associated with intestinal disease, and they are quick, robust, and cost-effective. To help you determine the appropriate chemical incitant for your studies, we describe some of the most commonly used agents below.

Types of Chemical Incitants

Dextran sulphate sodium: The most common option

Dextran sulphate sodium (DSS) is the most commonly used chemical agent to induce intestinal inflammation, and you can study both acute and chronic inflammation by adjusting the concentration and duration of DSS treatment. DSS works by direct and selective toxicity to intestinal epithelial cells. It causes a loss of surface epithelium, enabling luminal microbes and their metabolites to enter the lamina propria and induce an inflammatory response.

Trinitrobenzene sulfonic acid: Put it in ethanol

Trinitrobenzene sulfonic acid (TNBS) is primarily used to induce acute intestinal inflammation, but can also be used to establish chronic inflammation in mice and a variety of other animal models. TNBS stimulates an immune-mediated inflammatory response by producing hapten-modified self-antigens that are recognized by the host immune system. (Note that TNBS needs to be solubilized in ethanol to be chemically activated, which also helps to irritate the epithelial barrier).

As with other chemical agents, when using TNBS, consider the genetic background and phenotypic profile of your animal model.

Azoxymethane: Use it in combination

Azoxymethane (AOM) can be used in combination with DSS to enhance the severity of inflammation and induce chronic intestinal inflammation that progresses to colorectal cancer. Treating mice with DSS and AOM alters tissue cytokine profiles and increases the expression of IL-4 and IFN-γ, mirroring patients with ulcerative colitis. When used alone, AOM can induce cancer in the distal colon and disrupt several metabolic pathways such as MAPK intracellular signalling pathway and epithelial cell apoptosis.

Oxazolone: Its effects are rapid

Oxazolone is an effective inducer of acute inflammation, and it rapidly changes tissue architecture to induce tissue injury compared to other chemical agents. Its use in mice results in intestinal lesions associated with a predominant Th2 immune response as histological evidence shows an increase in IL-4, IL-5, and IL-13, cytokines. As with the other chemical agents mentioned, mouse strain can influence the effect of Oxazolone. For instance, BALB/c mice show increased tissue injury compared to C57BL/6 mice under the same oxazolone treatment.

Comparing Chemical Incitants

Biological Incitants: An alternative to chemicals

Similar to choosing the best animal model to investigate specific aspects of intestinal inflammation, choosing the most effective chemicals and biological agents to incite inflammation must be carefully considered. To accurately and thoroughly study intestinal inflammation, you’ll likely need to go beyond a single model and need to involve different animal models and different incitants to investigate a diverse range of disease mechanisms.

Compared with chemical incitants, biological incitants offer the advantage of being able to study both acute and chronic inflammation using agents that naturally cause inflammation in humans and non-humans. There is a plethora of biological incitants that you can employ that are generally classified as bacterial, protozoan, or helminth.

ProTips for selecting your incitant

Many host and chemical agent factors can impact the effectiveness of inducing tissue injury, as well as the severity of intestinal inflammation. As you determine which chemical incitant you should use, take the following factors into consideration:

• The molecular weight, concentration, manufacturer, and batch of the chemical agent
• The species, gender, and the genetic background of the animal model being challenged
• The method of administration—some chemicals work well to induce inflammation after ingestion, while others function best when applied via rectal administration
• Microorganisms present in the intestine and their interactions with the chemical incitant

Chemically induced mouse models of intestinal inflammation are critical tools for better understanding the pathophysiology of many inflammatory diseases. With MP Bio, you can consistently generate chemically induced mouse models of intestinal inflammation with high-quality DSS. Learn more about how to generate animal models for IBD by reading the Colitis Model Guidebook.