The process of inflammation involves the production of cytokines but also involves the release of free radicals with resultant oxidative stress, which actually can be a viscous circle of events, all playing a role in joint deterioration. Is it possible to reduce the production of these cytokines at their source or at a cellular level? The answer is yes, but it is somewhat complicated. We need to look at the problem from a systemic point of view, because that is where the problem lies. Considering the large number of cytokines being produced as a result of the inflammatory cascade, why not potentially target them at their source, instead of just trying to block their action? After all, inflammation is a systemic problem and in most instances, if there is one joint affected, there is another close by or potentially higher up in the leg or even the back that is taking extra pressure due to favoring or shifting of weight. IRAP therapy is a new tool in the medicine chest for equine veterinarians, but from my perspective may have some major limitations. Inflammation is an ongoing process and involves many cytokines, each with their own specific action. With each repeated injection comes the risk of bacterial infection and the act of sticking a needle into the joint actually spurs on the process of inflammation. It is reported that side effects to the IRAP are very low due to using blood from the patient as part of the therapy, which is good, however, we are still sticking a needle into the joint on weekly intervals. The other consideration of course is cost and potential side effects from therapy. Overall, the effects of IRAP are localized and impact only a small portion of the inflammatory cycle. By using IRAP therapy, we are also doing little to impact the production of IL-1 overall and systemically, IL-1 levels will likely be on the rise even though they may be blocked from exerting their action within that specific joint. Even though we may be able to block the receptors at which IL-1 attaches within the joint, we are doing very little to impact the production of the other destructive cytokines. For instance, there are other Interleukins that play a part in the cycle of inflammation and there are other cytokines such as MMP's (matrix metaloproteinases) that are responsible directly for cartilage erosion. As we have discussed in the past, inflammation involves several cytokines being produced and IL-1 is not the only one responsible for cartilage deterioration and pain production. IRAP therapy blocks the receptor in which IL-1 binds to within the joint, thereby in theory reducing inflammation, pain and further joint deterioration. It has been noted that horses requiring further injections tend to show a reduced response rate. Length of response rate is again variable, with most horses benefiting from results lasting 6-12 months, but then requiring either a booster injection or potentially a restart to the injection series. Effectiveness is variable and at the time of this writing, I am unable to find published research dictating response rates, but it has been reported that if there is going to be a response, it will be seen by the second or third injection. Cost can vary between clinics, but is reported to be between $1000 and $2500 for the complete series. In most cases, it is recommended to complete a three injections series, one week apart. Blood is withdrawn from the horse, incubated in a special syringe that helps to stimulate the IL-1 receptor blocker and then injected into the joint. IRAP therapy works on the principle of blocking the receptor at which IL-1 binds within the joint, thereby reducing inflammation and pain. As a result of ongoing inflammation, IL-1 is released by various types of cells and binds to receptors at other cellular locations to inflict action. Interleukin-1 is one of many cytokines, which act at many levels and are thought to be directly involved with cartilage loss. IRAP therapy is supposed to help manage the inflammation and joint deterioration more effectively through the use of the body's own natural resources.Īs we have discussed in prior blogs and emails, inflammation is a complex subject and involves the ongoing release of several cytokines responsible for cellular changes and deterioration. Therapies for joint disease in the horse now includes joint injections with corticosteroids, hyaluronic acid, polysulfated glycosaminoglycans and over the past several years, there is a new kid on the block termed IRAP or Interleukin-1 Receptor Antagonist Protein.
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