Role of macrophages on the benefits of oat beta-glucan on susceptibility to infection following exercise stress.

摘要

Exhaustive exercise has been associated with an increased risk for respiratory tract infection. Our laboratory has found that oat beta-glucan (ObetaG), a soluble fiber with mild immunostimulant activity, can offset the decrease in macrophage antiviral resistance and increased risk of infection associated with exercise stress. The purpose of these studies was to examine the role of lung macrophages on the benefits of oat beta-glucan on susceptibility to infection following exercise stress. Methods. Mice were assigned to exercise (Ex) or resting control (Con), and either H2O or ObetaG treatment. Exercise mice were run on a treadmill to fatigue (∼2.5h) for 3 consecutive days. ObetaG mice were fed a solution of ObetaG in their drinking water for 10 consecutive days. Mice were infected with HSV-1 via intranasal inoculation. In specific aim 1, mice were sacrificed 48h and 96h following infection and lung viral titers and cytokines were analyzed. In specific aim 2, lung macrophages were depleted using clodronate filled liposomes prior to intranasal inoculation with HSV-1 and were then monitored for morbidity, mortality and symptom severity for 21 days. In specific aim 3, lung and peritoneal macrophages were incubated with various concentrations of ObetaG and cytokine release was analyzed following in vitro HSV-1 infection. Finally, specific aim 4 involved measurement of cytokine release from lung and peritoneal macrophages following in vitro infection with HSV-1. Results. The benefits of ObetaG feedings on morbidity and mortality following HSV-1 infection in exercise stressed mice (shown in previous experiments) were also associated with a reduction in the increase in lung viral titers. Depletion of macrophages negated the beneficial effects of ObetaG on susceptibility to infection in exercise stressed mice. Both in vivo and in vitro ObetaG treatment resulted in an increase in cytokine release (IL-1beta, IL-6 and TNF-alpha) from both lung and peritoneal macrophages following HSV-1 infection in vitro. These data suggest that the benefits of orally administered ObetaG on susceptibility to infection in exercise stressed mice are at least partially mediated by lung macrophages. The specific functions of macrophages responsible for these effects are likely to include the release of pro-inflammatory cytokines.