The Harry M. Zweig Memorial Fund for Equine Research

Attenuating Exercise-Induced Immuno-suppression
in Athletic Horses

Dr. Dorothy M. Ainsworth

Infectious respiratory diseases are a major cause of reduced athletic performance and of horse wastage in the racing industry. In two recent multi-center studies undertaken by our laboratory, we found (1) that foals developing bacterial pneumonia had a reduced chance of racing as adults (Ainsworth et al, 1998) and (2) that only two thirds of racehorses with lung abscesses successfully returned to racing careers. Furthermore, the average convalescence period for racehorses with lung abscesses was 201 days for Thoroughbreds and 174 days for Standardbreds—a 6-month period of inactivity which represented a significant loss of earning potential (Ainsworth et al, 2000). Considering that the "window of opportunity" for a racehorse to successfully establish itself as a true athlete is relatively narrow (2 years), the development of pneumonia or pulmonary abscesses is a serious setback to the career or to the life of the horse. Thus, rather than simply treating these cases, our efforts must also be directed at preventing the development of infectious respiratory diseases in the equine athlete.

It has been well recognized that horses which race or perform strenuous exercise are at an increased risk for the development of bacterial pneumonia, pleuritis and lung abscesses (Raphel and Beech, 1982). It is believed that bacteria, which normally reside in the upper respiratory tract, are inhaled during exercise. This, in conjunction with exercise-induced suppression of the lung and systemic immune responses allows the bacteria to successfully establish lung infections or abscesses. A corollary to this is that current preventative health programs—vaccinations against the common respiratory pathogens such as influenza, equine herpes virus or even Streptococcus equi—may also be ineffective in the athlete because the exercise-associated immunosuppression prevents the development of an adequate, protective immune response.

In this proposal, (an extension of an existing study currently underway) we would determine whether immune system suppression in athletic horses performing high intensity treadmill exercise could be reversed or attenuated by using a commercially-available immunomodulator, EqStim®. While this drug currently enjoys widespread clinical use both in show horse and racetrack veterinary practices, there are absolutely no objective clinical data demonstrating efficacy. Indeed, there is the potential that such a drug might bias the immune system toward a deleterious response (allergy) or because of inducing a secondary fever spike, cause the horse to go off feed and water! As there is increasing discussion in the horse circles of simply administering the immunomodulator before shipping horses long distances, or of using it intratracheally as a prevention for exercise-induced pulmonary hemorrhage, it becomes critical that an objective evaluation of this pharmaceutical agent be undertaken by an independently supported laboratory (not a laboratory financed by the drug company that would influence the release of negative results).

In this study, we would specifically determine if pre-treatment of horses in race-fit condition (and undergoing strenuous exercise) with the immunomodulator does indeed improve their ability to generate antibody and cytokine responses to a nebulized vaccine. The response of the group of horses treated with the immunomodulator would be compared to the responses of exercised and sedentary horses receiving only the nebulized vaccine (Study currently underway). The study is a logical one given our recent preliminary data demonstrating a down-regulation of interferon gamma levels in pulmonary immune cells of exercised horses. Interferon-gamma is a cytokine or protein that is critical for immune system function. It promotes immune cell killing and phagocytosis of bacteria, viruses and protozoa as well as the production of appropriate types of antibody needed to combat infections. The decrease in interferon-gamma levels that we have documented in exercised horses (which is not evident in sedentary horses) using sensitive molecular biology techniques provides scientific evidence of why athletic horses are prone to developing respiratory tract infections. We are now in a position to objectively evaluate the efficacy of the immunomodulator on reversing or attenuating the down-regulation of interferon gamma in athletic horses.

Our study is unique in several aspects: First, it represents a collaborative effort of three laboratories at Comell University which will employ advanced techniques in immunology (enzyme-linked immunosorbent assays) and molecular biology (polymerase chain reactions) to investigate a clinically-relevant problem. Secondly, using these methodologies, we would document alterations in both the amount of antibody produced against this "vaccine", as well as in the amount of immune-regulatory proteins (cytokines) produced by the immune cells. This latter initiative is especially relevant because it has been shown in human medicine that the ability or inability to generate certain cytokines or cytokine patterns in response to an infection, often determines the clinical course of the infection (Lucey et al, 1996; Watkins et al, 1995). Thirdly, the results of this study would immensely improve our understanding of the potential mechanisms of immune system modulation, results that are directly applicable to the treatment of a wide variety of respiratory tract disorders in horses.