Immunostimulants boost the immune system to fight disease

by Denise Steffanus

THE NEW buzzword in veterinary medicine is immunostimulants--products that heighten the body's natural immune response.

For years, veterinarians have been concerned about the overuse of antibiotics. Immunostimulants may help turn the trend away from use of drugs in some situations and direct it to more natural ways to fight disease. Their use as a preventive also can fortify the immune system to enable horses to avoid becoming ill.

Elizabeth Davis, D.V.M., Ph.D., explored immunostimulants as part of her doctoral dissertation and in studies conducted at Kansas State University, where she is an assistant professor of clinical sciences. Davis said immunostimulants are ideal for use prior to any situation when a horse's immune system may become depressed or when it may be challenged by exposure to disease.

"These would be things like prior to long-distance transport, which typically is classified as greater than 500 miles," Davis said. "In some settings, prior to weaning would be considered as a stressful event, and sending a young horse to a training stable."

Davis also has used immunostimulants successfully in helping horses to recover from a bout of disease.

"Many times, it might be a bacterial or a viral disease," she said. "The horse is in the recovery phase, but it is just lingering. I like to go ahead and boost those horses."

Other uses for immunostimulants are to shorten the course of warts in young horses; resolution of reproductive infections in mares; and as an aid in eradication of equine sarcoids, which are skin tumors spread by biting flies.

West Nile virus

Viruses present a unique challenge to doctors and veterinarians. Unlike a bacterial infection that can be treated with antibiotics, most viruses simply must run their course. So healers can do little more than treat the symptoms and provide care to support the patient's body while its immune system fights the virus.

Over the past few years, Bonnie Rush, D.V.M., M.S., head of equine medicine and surgery at Kansas State, has been using an immunostimulant to treat horses with West Nile virus. Because no antiviral drug has been found to be effective against the disease, which has a 40% mortality rate in horses that show

clinical signs, Rush turned to interferon-a, a naturally occurring protein, to boost the ailing horses' immune systems to mount a better fight against the virus. In low doses, interferon-a enhances the immune system's ability to fight disease. In high doses, it acts as an antiviral.

Interferon-a also has anti-inflammatory properties, which means the treating veterinarian may be able to reduce the use of anti-inflammatory drugs. For treatment of West Nile virus, the clinicians at Kansas State administer high doses of interferon-a.

Looking back, Rush said she is pleased with the results she achieved with the novel treatment.

"Interferon-a is still the treatment I would recommend," she said.

Immunostimulants have shown promising results in fortifying a mare's immune system to naturally destroy Streptococcus, bacteria that cause inflammation of the lining of the uterus. Called endometritis, the condition often affects a mare's fertility by preventing her from conceiving or causing her to lose the fetus in early gestation if she does become pregnant. Persistent, unchecked endometritis also can cause scarring and degenerative changes in the uterine lining.

Settle, manufactured by Bioniche Animal Health USA, is the first immunostimulant to be approved by the United States Department of Agriculture as an aid in the treatment of endometritis.

"Settle is one of the newer immunostimulants on the market," Davis said. "It does look like it stimulates the immune system effectively and helps susceptible mares clear uterine inflammation."

Sales and training

Young horses are faced with a formidable challenge to their immune systems when they leave the farm for the first time to travel to sales, training centers, or racetracks, putting them at high risk for illness.

•Their naive immune systems encounter pathogens to which they previously have not been exposed;

•The first trip on a van or trailer usually is stressful psychologically and physically;

•The pace at sales often is hectic and grueling for young horses;

•Training is stressful and physically demanding; and

•The large horse population and high traffic in and out of sales, training centers, and racetracks facilitates the spread of disease.

Immunostimulant therapy that starts before young horses leave home will help fend off disease and, if they do become ill, may reduce the severity of symptoms and shorten the course of the illness.

According to Cornell University researcher Dorothy M. Ainsworth, D.V.M., Ph.D., racehorses often suffer from exercise-induced depression of the immune system, which can cause lung infections or abscesses when the horse breathes bacteria into the lungs and the immune system fails to launch a good antibody response against it.

"Exercise-associated immunosuppression also enables viral infections to become established in the respiratory tract, which, in turn, predisposes [the horse] to the development of secondary bacterial infections," Ainsworth said. "Theoretically, if this immune suppression could be reversed or attenuated, the prevalence of infectious pneumonia, bronchitis, or lung abscessation should dramatically decrease in the equine athlete."

At Kansas State, Davis successfully resolved lingering respiratory infections by administering a three-dose course of the Neogen Corp. product EqStim to fortify the horse's fatigued immune system.

"EqStim is one that I do like to reach for," she said. "We have a fair bit of data that we've generated on it at Kansas State University."

Davis also has been successful in treating inflammatory airway disease with low-dose interferon-a.

Blood work first

Davis warned that immunostimulants should not be used when a horse's immune system already is operating at maximum levels, "smack-dab in the middle of a challenge," she said. "So, if we have a horse that has very severe pneumonia, peritonitis, or any serious gastrointestinal disease, we're probably not going to utilize an immunostimulant at that time."

In certain situations, Davis said it is prudent to perform blood work on the horse to determine the status of its immune response before administering an immunostimulant.

"If it is a horse that is getting ready to travel across the country and it is apparently healthy, it is probably very reasonable to go ahead and initiate the immunostimulant therapy without relying on blood work," Davis said. "But if it is a horse that is sick, absolutely, I would want to do some blood work beforehand."

A high white-cell count shows the horse is mounting a good immune response, while a normal-to-low white-cell count indicates the horse's immune system has been compromised.

Because an immunostimulant should be used only under veterinary supervision, Davis advised horsemen to rely on the treating veterinarian's recommendations as to when use of an immunostimulant would be indicated, which product would be most effective, and whether blood work should be performed before starting a course of treatment.

Davis also stressed that some immunostimulants, such as certain types of interferon-a, should not be given repeatedly because the horse's immune system would begin to create antibodies to destroy it because it is a foreign protein.

"But it is uncommon that we would have to give it time and time again if we had the diagnosis right," she added.

Other immunostimulants developed from bacteria that are harmless to horses, such as EqStim, which is derived from the bacteria that cause acne in humans, are safe and effective for repeated use. "EqStim is not going to be a problem; every time you give that, it is still going to be effective," Davis said.

Davis said immunostimulants rarely cause adverse side effects, other than a mild fever. "We're seeing the immune system do what we want it to do, so that is why we might see a fever spike, which is usually mild, self-limiting, and in the range of 102¡ to 102.5¡. EqStim is labeled to be administered in three doses, and I sometimes see a fever after the second or third dose."

As with any medication, a horse may be hypersensitive to an immunostimulant, which makes it doubly important that a veterinarian administer the immunostimulant and monitor the horse for signs of distress. "Then, if there is a problem, the veterinarian can treat it quickly and effectively," Davis said. "Those reactions, fortunately, are very minimal."

Davis advised horsemen to discuss the possibility of using immunostimulant therapy with their veterinarians.

"There are several products on the market, and they probably each--and particularly those that have a USDA label--are going to have their place in veterinary medicine," she said.

Denise Steffanus is a contributing editor of Thoroughbred Times who writes frequently on veterinary and farm management topics.