Veterinary researchers will test common human medicines to identify histamine’s role in early-life inflammatory responses that impact long-term health and development in production animals.

Dr. Adam Moeser, Matilda R. Wilson Endowed Chair for the College of Veterinary Medicine’s Department of Large Animal Clinical Sciences, received a $630K grant from the United States Department of Agriculture’s National Institute of Food and Agriculture (USDA NIFA) to test histamine-blocking interventions that may help mitigate inflammatory responses due to early-life stress.

Specifically, Moeser and his team will administer Claritin® and Pepcid AC® to pigs before they are weaned.

“Pigs and other food animals endure numerous stressors during early stages of life due primarily to management practices. Among these stressors, weaning is the most challenging event for a pig during this period,” Moeser says.

That stress creates a high level of intestinal inflammation during a critical period of the pigs’ development. Moeser’s previous work has highlighted the long-term effects of weaning stress on how the immune system and gut develop. Now, he’s conducting research to find evidence that the inflammation can change how the pig’s gastrointestinal and immune systems develop, which puts the animals at higher risk for disease and poor performance throughout their lifespans.

What also remains unclear is exactly how the inflammatory response begins. Without this knowledge, there are limitations in scientists’ ability to develop, adapt, or repurpose therapeutics and other interventions aimed at protecting the animals in the short term while fostering their long-term health.

This, ultimately, is Moeser’s goal. To achieve it, he’s experimenting with familiar drugs: Claritin®, an over-the-counter antihistamine commonly used for allergies, and Pepcid AC®, an over-the-counter stomach acid reducer.

“Through our research, an intriguing finding emerged–the levels of histamine in the blood and gastrointestinal tracts of pigs increased to extremely high levels immediately after experiencing stress,” explains Moeser.

Mast cells are the immune cells that orchestrate the body’s stress response; they release mediators like histamine as part of that response, which can cause inflammation. Moeser explains, “This discovery prompted us to explore the implications of this response for animal health by investigating the effects of histamine blockers.”

Claritin® is a histamine 1 receptor antagonist, and Pepcid AC® is a histamine 2 receptor antagonist. Histamine receptors are present on a wide range of cells throughout the body; by blocking these receptors with these medications, the inflammatory response triggered by histamine can be prevented.

Moeser and his team will administer those drugs to the pigs prior to stress (weaning). After the stress, they’ll measure how those drugs impact the pigs’ inflammatory responses, as well as any changes to gastrointestinal physiology and function.

While medications like Claritin®and Pepcid AC® have long been established for their respective purposes, their potential application in mitigating GI inflammation remains largely uncharted territory. Additionally, the team’s investigation of interventions during the critical developmental stage of pigs, with the aim of enhancing disease resistance and health in the long term, adds a unique aspect to their study.

“In the realm of animal health, the exploration of histamine as a target for gastrointestinal inflammation is a relatively new focus,” says Moeser.