It makes sense to state that a horse with a weakened immune system is more susceptible to infections. And usually this is true, but it’s not likely the case with EPM. Several studies with horses and mice show that a suppressed immune system — whether induced or due to an immune-system disease — may actually somehow protect the horse from EPM symptoms. In fact, stimulating the immune system the wrong way may make things worse.
In 2001, a study (Sanville et al) reported that horses stressed by transport prior to being fed the EPM organism developed more severe symptoms. This part of the report fit well with the idea that suppressed immune responses are involved in horses that contract EPM. However, in that same study, horses given a single dose of the corticosteroid dexamethasone — an immunosuppressant — at the same time as the infectious dose of the EPM organism showed the least severe signs of the illness. What’ The horses with a suppressed immune response did better’
Also in 2001, a study appearing in Veterinary Parasitology found that horses given dexamethasone after being fed the EPM organisms developed antibodies to the organism just as well as horses not given the drug, if not faster. There was no difference between the groups in symptoms, and 90% of the infected horses showed similar signs of inflammation in their brains. However, none actually had the organism present in the brain on postmortem exam. In other words, horses were no worse off with the dexamethasone suppressing their immune system than those without it.
Perhaps the most startling finding to date is a 2004 study from Washington State. It showed that Arabians with SCID (severe combined immunodeficiency, a genetic immune-deficiency syndrome) that were infected with Sarcocystis neurona (the EPM organism) developed no neurological signs of the disease and had no evidence of the infection in their nervous system on postmortem. The horses did show prolonged high levels of the parasite in their blood as well as in other body tissues (e.g. muscle, liver), but EPM never developed. A similar thing happened with mice studied by the Washington group.
So what does all this mean to owners trying to battle EPM’ Those little mice may eventually give us the answer. So far, it’s known from mice studies that a key compound in wiping out the EPM organisms is INF-gamma, a type of interferon. INF-gamma can be produced by both neutrophils and lymphocytes. Since the SCID mice have defective lymphocytes, they tested what would happen if SCID mice also had their neutrophils knocked out. Amazingly, the result was the same: No EPM.
Attention is now being directed back to the lymphocyte arm of the sophisticated immune response and to other nonspecific anti-infection molecules like interferon to see what it is that horses susceptible to EPM may have (or lack) that makes them vulnerable. For example, researchers working with lymphocytes from normal and EPM-infected horses have found that those with EPM do not respond normally to proteins from the organism, although they do have a normal response to other triggers. The neurological invasion may result from a combination of this very specific weakness in their immune response and overcompensation by other areas.
While stress is a risk factor for EPM — and virtually any horse may be infected if the dose of organisms ingested is large enough — stimulating the immune system may not be the way to go in an EPM horse. Horses and mice with severe combined immunodeficiency appear to be protected from EPM, and normal horses given the immunosuppressing steroid dexamethasone are no worse off.
Until we know the specific immune system cellular messengers involved in keeping EPM out of the nervous system and generating an effective immune response to kill them, stimulating the immune system in the wrong way could make things worse.