Searching for New Treatments for Systemic Inflammatory Response Syndrome

Systemic inflammatory response syndrome (SIRS) occurs when the immune system overreacts, or "goes haywire.” SIRS is associated with many conditions including severe infections and major trauma, and can lead to higher treatment costs, organ failure, laminitis and even death in equine patients. Horses with both colic (gastrointestinal disease) and SIRS are eight times more likely to die than horses with colic and without SIRS. Unfortunately, effective treatments for SIRS in horses are lacking. One of the dysregulation pathways noted in horses with SIRS concerns insulin and blood sugar levels. In humans and other animals, the drug metformin has shown promise in improving SIRS. It can work to both control the balance of insulin and blood sugar levels as well as regulate the immune response. Metformin is safe, affordable, and has long been used in horses to treat insulin dysregulation in another common disorder, equine metabolic syndrome. However, its effects on equine immune cells and in SIRS are not known. In this project, researchers will explore the use of metformin as a new SIRS treatment in horses. The team will study how metabolic and immune markers correlate with SIRS and disease severity in horses admitted to referral hospitals for colic treatment. They also will investigate metformin’s effects in a safe, simulated SIRS model under laboratory conditions. Findings will provide key information about how the metabolic and immune systems interact in horses with SIRS. If successful, this new information will help inform the development of a new treatment for this potentially fatal condition in horses.