Eyeing Up IRAP


irap

This emerging therapy for horses, can enhance the body’s ability to help itself.

Over the last decade or so, numerous advances have been made in the field of equine orthopedics. The options for treating traumatic and degenerative joint disease are no longer limited to anti-inflammatory drugs and intra-articular steroid injections.

Autologous therapies such as platelet rich plasma (PRP), stem cell therapy, and IRAP have become familiar to many horse owners and are used in conjunction with, or in place of, more traditional treatments. IRAP, or interleukin-1 receptor antagonist protein, provides many of the anti-inflammatory effects of other intra-articular treatments, but without many of the detrimental side effects.

A Bit of History

IRAP was discovered in the 1980s in human leukemia patients. It was found to decrease the effects of an inflammatory cytokine called interleukin-1 (IL-1). IL-1 has been identified as an important player in the inflammatory process in osteoarthritic joints. It has been shown to increase cartilage matrix degradation by up-regulating the pro-inflammatory mediators and proteolytic enzymes that break down cartilage and decrease its repair by down-regulating the production of cartilage macromolecules. Furthermore, IL-1 is thought to be involved in osteophyte production (boney proliferation seen in osteoarthritic joints).

IRAP blocks the effects of IL-1 by acting directly on the IL-1 receptor in cells and inhibiting IL-1 attachment to the receptor. The source of IRAP was found to be particular types of white blood cells, monocytes and macrophages. By culturing monocytes, IRAP production could be induced.

Since the protein is produced in the body naturally, IRAP was immediately considered an exciting discovery. It had the potential to produce anti-inflammatory effects without the risk of the immune-mediated reaction and other side effects associated with intra-articular injection of manufactured medications.

Production Process

The process of producing IRAP for use in horses takes about 24 hours. Approximately 50 mls of blood are drawn into a syringe filled with borosilicate glass beads. The interaction of the horse’s monocytes with the glass beads is meant to induce IRAP production by the cells. The procedure is performed using sterile techniques to avoid any contamination, as the final product will be injected back into the horse. The syringe is then placed in an incubator for about 24 hours at 37ºC (98.6ºF), which allows time for the monocytes in the whole blood to produce increased amounts of IRAP.

The blood is then centrifuged to separate the blood cells from the serum, and filtered to remove any cells and debris. The final product that we generally call “IRAP” is more appropriately termed autologous conditioned serum (or ACS), as it contains much more than just pure IRAP. It also contains growth factors released from platelets during the serum processing, as well as other pro- and anti-inflammatory cytokines including IL-1. The final product is separated into aliquots for multiple injections (2 ml to 4 ml depending on the site to be treated) and frozen at -20ºC (-4ºF) for preservation, to be used in the future.

More Studies Needed

Although IRAP therapy is regularly used in the equine veterinary practice, few controlled studies have been completed. A study at Colorado State University assessing the efficacy of intraarticular IRAP/ACS treatment used horses with carpal (knee) chip fractures. The horses were treated with either ACS or saline for four treatments at one-week intervals, starting two weeks after the initial insult. The ACS-treated group showed significantly decreased lameness grades at ten weeks after the injury as compared to the saline-treated group.

Although not commercially available at this time, IRAP gene therapy has already been studied in horses. Scientists created a viral vector that can be injected into a joint to carry the IRAP gene into the horse’s cells. Once incorporated into the cells, the gene up-regulates natural IRAP production in the joint, thereby producing anti-inflammatory effects.

IRAP Benefits

IRAP is typically used in synovial structures including joints, bursas and sometimes tendon sheaths. The typical protocol uses sterile techniques to inject an IRAP aliquot into the affected area every one to two weeks for three to four treatments. Rest periods of five to seven days are typically recommended following each treatment. Improvement of the lameness condition is generally expected after two treatments, with additional improvement after the third and fourth injections. IRAP is not typically injected into soft tissue lesions (such as tendon or ligament tears), although some practitioners and researchers are looking into this possibility.

IRAP is most often used in cases of mild to moderate arthritis, and sometimes post-operatively following arthroscopic procedures. It is especially helpful when a horse has previously had adverse reactions to intra-articular injections with steroids and/or hyaluronic acid. Since the IRAP is derived from the horse’s own blood, the risk of immunemediated reactions are greatly reduced.

IRAP is also used regularly in competition horses to avoid the use of prohibited substances such as steroids. Steroids are not only disallowed in regulated competitions, but they also have some negative effects on articular cartilage and should not be used on a regular basis. IRAP allows more frequent treatment of an osteoarthritic joint, and therefore may provide a more effective treatment. In fact, IRAP has become the therapy of choice for some practitioners when steroid therapy no longer seems to work in equine patients.

Given the time and equipment required for IRAP processing and multiple injections, the therapy is relatively expensive. Broadly, the cost to draw, process and then inject IRAP will be somewhere in the $1,000 to $1,500 range. However, the idea of an autologous product with such potent antiinflammatory effects is very exciting.

As more research on the efficacy and action of IRAP and ACS is published, the therapy is likely to become more common and benefit a larger proportion of our equine population.


Two IRAP Systems Available

Two different IRAP systems are available, both of which use the same basic technique as described in the article. They include irap® (available through Dechra Veterinary Products), and IRAP™ II (manufactured by Arthrex).

Recent studies have shown that the concentration of IRAP in the ACS produced by the IRAP™ II system is significantly higher than in the irap® system, although it also has more IL-1. Interestingly, whole blood that is simply incubated for 24 hours has increased amounts of IRAP as well, similar to the levels found in the ACS produced by the irap® system.


References:

Textor, J. “Autologous Biologic Treatment for Equine Musculoskeletal Injuries: Platelet-Rich Plasma and IL-1 Receptor Antagonist Protein”. Vet Clin Equine, 2011; 27: 275-298.

Caron JP. “Osteoarthritis”. In: Ross MW, Dyson SJ, Eds. “Diagnosis and Management of Lameness in the Horse”. Elsevier Science, 2003; 579-580.


A. Rachel Roemer, DVM is an associate veterinarian in the Field Service division at New England Equine Medical & Surgical Center. She grew up in Massachusetts, where she began her riding career at a local hunter/jumper barn. Since then she has competed in dressage and eventing disciplines and was an IHSA member through college. Dr. Roemer graduated from Brown University with a degree in biology and went on to receive her D.V.M. from Cornell University. Dr. Roemer has a particular interest in lameness and the performance horse, but also enjoys all aspects general ambulatory practice.

D. Michael Davis, DVM, MS is the founder and CEO of New England Equine Medical & Surgical Center located in Dover, NH. He grew up in upstate NY horse country, heavily involved with horses foxhunting and eventing. Dr. Davis received his B.S. degree in Animal Science and D.V.M. from Colorado State University. From there, he attained an M.S. degree and completed a residency in Equine Surgery at Louisiana State University. Dr. Davis has now practiced in New England for over 20 years. He sees a variety of cases, including lameness and imaging, elective and emergency surgical cases and assesses horses for other causes of poor performance. Newenglandequine.com

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