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It’s All Connected: Bodywide Inflammation in Horses

By Nancy S. Loving
Here’s what researchers are learning about bodywide inflammation’s effect on horses
hen you hear the term inflammation, you might picture a localized swollen area on a limb or around a wound. But inflammation also occurs systemically, affecting the whole body. It has been a buzzword in the medical community for years in discussions on how to manage chronic diseases in humans. Equine researchers have begun studying the concept of whole-body inflammation because of its links to a variety of health problems, including equine metabolic syndrome, insulin resistance, and laminitis; “leaky gut syndrome”; and risk of musculoskeletal injury.
How does bodywide inflammation even occur? Well, if the body’s normal protective responses become amplified, what started as a defense mechanism can turn into a chronic problem. The immune system normally secretes pro-­inflammatory cytokines, which are chemical messenger proteins such as interleukins (IL) and tumor necrosis factor (TNFα). These substances are important for initiating a physiological response to infections or injury and seeing to a successful recovery.
While inflammation might start in one tissue, excessive inflammation releases substances into the circulation that act systemically on other tissues throughout the body. Let’s look at some of the negative effects this process can have.
Obesity, Insulin, and Inflammation
Energy sources such as glucose—which horses obtain from consuming ­carbohydrates—can negatively affect the horse’s endocrine system if not used or stored in the body’s tissues properly. This can lead to bodywide inflammation. 
“When an animal is sick and off feed, there is continued need to preserve glucose for tissues that require it, such as the brain,” says Jessica Suagee-Bedore, PhD, assistant professor of equine science at Sam Houston State University, in Huntsville, Texas, who has a special interest in obesity and insulin resistance in horses. “TNFα is important for initiating insulin resistance that is beneficial in the face of illness. However, the body doesn’t differentiate between cytokines released to initiate the sickness response or cytokines released due to diet or obesity. Therefore, insulin resistance develops when an animal consumes a diet that promotes inflammation, such as high-starch and -sugar feeds, or in an animal that already experiences high levels of inflammation due to obesity.”
The association between inflammation and obesity depends on factors such as breed, exercise, diet, and aging—often referred to as inflammaging. We now know that older horses naturally have higher circulating concentrations of cytokines, namely IL-6 and TNFα.
“One chief concern of an animal’s body is the prevention of hyperglycemia (elevated blood glucose levels) or hypoglycemia (low blood sugar levels), as either of these can lead to a host of physiological problems,” says Suagee-Bedore. For example, hyperglycemia results in inflammatory free radical production that damages tissue. Normally, the body stores any extra glucose in the appropriate tissues after eating. Skeletal muscle and the liver take up most of the glucose, converting it to glycogen the body can use for energy later on.
When this system goes awry, cells become less able to respond to the insulin hormone transporting glucose from the bloodstream into storage tissues. Suagee-Bedore compares insulin resistance development to falling dominoes, with insulin being the signal that tips off the first domino.
“For a healthy horse, the dominoes fall in a line, but in an insulin-resistant horse, one domino is slightly braced and doesn’t completely fall over,” she says. “More insulin has to keep hitting it to get it to tip.”
Without weight loss and exercise, affected horses remain insulin-resistant for prolonged periods. “Ultimately, it seems there is a positive feedback cycle, with insulin resistance resulting from inflammation and also promoting it bodywide,” she says.
She explains it like this: “Adipocytes (fat cells) secrete all sorts of cytokines, which have the same roles in initiating insulin resistance and disrupting metabolism as they would if they were secreted by the immune system during a bout of illness. In a normal healthy animal, these cytokines are synthesized and released but function to regulate metabolism. Fat cells enlarging with obesity synthesize greater amounts of cytokines to disrupt metabolism in adipose tissue (another key energy reserve) and skeletal muscle. This leads to development of insulin resistance. In response, the pancreas secretes more insulin to signal muscle cells to take up glucose for the critical task of preventing hyperglycemia. Additionally, adipose tissue harbors macrophage white blood cells, which as part of the immune system produce and secrete cytokines.”
There is a great deal of “cross-talk” between macrophages and adipocytes, she adds.
Originally, Suagee-Bedore thought glucose or insulin in the bloodstream signaled cells to synthesize inflammatory mediators. “During glucose and insulin intravenous infusion studies, we see some increase in circulating and tissue level inflammation,” she says.
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