New study shows direct, beneficial effect of short-term moderate exercise on susceptibility to upper respiratory tract infection

November 10, 2003 - (Bethesda, MD) �?Americans are lining up for flu shots, stocking up on cough and cold medicines, and taking inventory of what antibiotics they may again need this winter. Despite expansive planning, few remember two low-tech staples that can be easily and affordably added to their first line defenses against the illnesses of the season: exercise and oat fiber Beta-Glucan (β-glucan).

Individually, moderate exercise and the soluble oat fiber β-glucan increase immune function and decrease the risk of infection. However, no information exists about the possible benefits of combining the two. A new study, using an animal model of induced respiratory infection, looks at the direct effects of a short period of moderate exercise training and consumption of soluble oat fiber β-glucan on the illness (morbidity) and death (mortality) following exposure to an upper respiratory tract infection (URTI). The study concludes that that moderate exercise alone is associated with a significant reduction in risk.

Background: How It Works

Exercise - It was thought that moderate exercise may enhance resistance to infection by activating the release of immunostimulatory factors (such as growth hormones, prolactin and cytokines), which in turn activate various immune cell populations.

Exercise bouts of moderate duration (<60 min) and lower intensity (<60 %VO2 max) have been associated with enhanced activity of immune parameters, including macrophage chemotaxis, oxidative metabolism and phagocytic activities, as well as increased natural killer (NK) cell activity. These cells may constitute an important part of a first-line defense against URTI by nature of their phagocytic, cytotoxic and intracellular killing capacities.

Oat Fiber β-Glucan - β-Glucans (polysaccharides derived from the cell wall of yeast, fungi, algae and oats) have been shown to enhance the activities of both the non-specific and specific immune system but have received little attention in the field of exercise immunology. β-Glucan exerts its effects through the direct stimulation of macrophage, neutrophil and NK cells via β-glucan specific receptor sites. When bound, β-glucan activates key cells, which set off a cascade of immune defenses that protect the organism from various viral, bacterial and fungal challenges. The exact mechanisms are at least partially dependent on the route of administration; protection following oral administration results primarily from certain effects of ingestion, for example.

A New Study

The authors of a new study, entitled “Effects of Moderate Exercise and Oat β-glucan on Innate Immune Function and Susceptibility to Respiratory Infection,�?are J.M. Davis, E.A. Murphy, A.S. Brown, M.D. Carmichael, A. Ghaffar and E.P. Mayer, all of the University of South Carolina, Columbia, SC. Their findings are published in the online edition of “Articles in Press�?for the American Journal of Physiology �?Regulatory, Integrative and Comparative Physiology. The journal is one of 14 scientific periodicals published each month by the American Physiological Society (APS).

Methodology

The researchers used the following protocol:

Mice: Male CD-1 mice, four weeks of age, were acclimated at the research facility 3+ days prior to experimentation. They were maintained on a 12:12-hour light-dark cycle in a low stress environment and given food (chow) and water (oat â-glucan dissolved in water) ad libitum. Separate groups of mice were used for each dependent variable: in vivo susceptibility to infection (n=24 per group), macrophage anti-viral resistance (n=18 per group), and natural killer (NK) cell cytotoxicity (n=12 per group).

Nutrient Treatment: Mice were randomly assigned to one of four groups: exercise water (Ex-H20), exercise oat β-glucan (Ex-OβG), control water (Con-H20), or control oat â-glucan (Con-OβG). Ex-H20 and Con-H20 received tap water for the ten days prior to inoculation/death, while Ex-OβG and Con- OβG mice were fed a solution of oat β-glucan dissolved in the drinking water for the 10 days prior to inoculation/death. Oat β-glucan was not fed to the animals during the 21 days following inoculation.

Treadmill Acclimation and Exercise Protocol: On the second day of oat â-glucan/water treatment, exercise mice (Ex-H20 and Ex-OβG) were acclimated to a treadmill for 20 min/day. The exercise protocol consisted of a one-hour bout of treadmill running for six consecutive days. Mice in the control groups (Con-H20 and Con-OβG) remained in their cages in the treadmill room during the bouts.

Intranasal Inoculation of and Infection with HSV-1: Intranasal inoculation of Herpes simplex virus type 1 (HSV-1) VR strain was administered. This strain in the mouse is an established experimental model of respiratory infection; this route was chosen to mimic the typical route of entry for viral infection.

On the day of the experiment mice (n=24 per group) were exposed to either control treatment or exercise for one hour and immediately returned to their cages. Fifteen minutes later they were anesthetized and inoculated intranasally with 50 ìL of HSV-1 VR strain. Following infection, the mice were returned to their respective cages and monitored twice daily for 21 days for signs of morbidity/mortality.

Peritoneal Macrophage Antiviral Resistance: On the day of experiment, mice (n=12 per group) were exposed to either control or exercise treatment. Immediately following exercise or rest they were euthanized. Peritoneal macrophages were collected, prepared and infected with HSV-1. The virus was allowed to absorb for 90 minutes and, 72 hours after infection, anti-viral resistance was quantified.

NK Flow Cytometric Assay: On the day of experiment, mice (n=12 per group) were either exposed to control or exercise treatment and euthanized 30 min/post-treatment. Spleens were removed and weighed, and blood cells were immediately lysed. Two parameter flow histograms were conducted.

TNF-β and Statistical Analysis: Blood was collected and plasma assayed for TNF-β. Statistical analyses were performed for differences in morbidity and mortality across the 21-day post-infection period. Differences in NK cell activity, macrophage anti-viral resistance, TNF-β, weight gain and fluid consumption were compared using a two-way analysis of variance.

Results

Highlights of the findings include:

�?Morbidity: There were differences in morbidity across the groups over the 21-day post-infection period. Intranasal administration of HSV-1 following short-term moderate exercise training resulted in a decrease in morbidity as compared with resting controls. Exercise mice (Ex-H20) experienced only a 13% incidence in morbidity while 58% percent of control mice (Con-H20) exhibited such symptoms. Consumption of oat β-glucan for ten days prior to inoculation did not further decrease the symptoms of morbidity as there was no real difference between the Ex-H20 group (13%) and the Ex-OβG group (21%).

�?Mortality: Similar effects were found for mortality over the 21-day post-infection period among the four groups. Intranasal administration of HSV-1 following six days of moderate exercise resulted in a decrease in mortality compared to control mice. Ex-H20 mice showed a mortality rate of 8% over the 21-day period compared with a 46% rate among the Con-H20 mice.

Consumption of oat β-glucan for ten days prior to inoculation did not further decrease mortality in the exercise animals; there were no significant differences between Ex-H20 and Ex-OβG mice. However, oat β-glucan administration did show a trend toward decreasing mortality in the control mice, prolonging the survival time of resting animals. Con-H20 mice showed a mortality rate of 46% while Con-OβG mice experienced a mortality rate of only 33%.

�?Peritoneal Macrophage Anti-Viral Resistance: The intrinsic anti-viral resistance in mice exercised moderately for six days (Ex-H20) was significantly greater than in control mice (Con-H20). Oat β-glucan consumption for ten consecutive days did not further enhance the benefits of exercise. However, resting mice consuming oat β-glucan dissolved in the drinking water for ten days prior to death (Con-OβG) had a significantly greater macrophage anti-viral resistance than did resting mice drinking water (Con-H20).

�?NK Cytotoxicity, TNF-a: Six days of moderate exercise was associated with a very small increase in splenic NK cytotoxicity at effector:target ratios of 5:1 and 1:1, but not at 20:1 and 80:1, compared with non-exercised controls. Oat β-glucan consumption did not result in any change in NK cytotoxicity. The presence of TNF-á was not detectible above 3 pg in any of the groups following moderate exercise or oat β-glucan treatment. Therefore, moderate exercise or oat β-glucan consumption was not associated with an elevation of this cytokine.

Conclusions

These results support the hypothesis that moderate exercise training can decrease susceptibility to induced respiratory infection in mice. These data also provide evidence of a role for macrophages and NK cells as mediators of this benefit on host protection. While there were no added benefits of oat β-glucan in this experiment, it deserves further research to evaluate the positive trends observed in both the immune function and infection rates.

Source: Online edition of “Articles in Press�?for the Journal of Applied Physiology.

The American Physiological Society (APS) was founded in 1887 to foster basic and applied science, much of it relating to human health. The Bethesda, MD-based Society has more than 10,000 members and publishes 3,800 articles in its 14 peer-reviewed journals every year.

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