Innate Immune Response to Exercise and Physical Activity

Neutrophils

As described in Chap. 1, ageing is characterized by reduced neutrophil phagocytic capacity, chemotaxis, ROS production and extracellular trap formation. However, despite the well characterized dysfunctions with age, less is known about the effects of exercise on neutrophil function in the aged human.

Elevated neutrophil counts accompany increased inflammation with age and the increased ratio of neutrophils to lymphocytes is associated with many age-related diseases including cancer [7]. Compared to more active individuals, less active and overweight individuals have higher circulating neutrophil counts [8]. Six weeks of cycling exercise, 1-6 times per week at around 80-90 % of aerobic capacity (У02таХ) was associated with reduced neutrophil counts in women over 50 years old [8]. Furthermore, long-term exercise training of around 80 minutes per day, 5 days per week in those over 70 years resulted in lower neutrophil counts than age-matched non-exercising individuals [9]. Although these studies suggest an intervention and years of exercise training can reduce neutrophil numbers the data are not consistent [10,11].

More likely is that neutrophil numbers, with no obvious disease state, are homeostatically maintained in relation to body mass. In overweight individuals, aerobic exercise training can reduce neutrophil numbers, which is associated with glucose homeostasis and body fat content [8, 12]. These data suggest that neutrophils are susceptible to inflammatory perturbations associated with the metabolic consequences of a positive energy balance and that exercise training can impact neutrophils by improving energy balance and glucose homeostasis [13] . Indeed, poor neutrophil function is associated with increased fasting glucose levels [14]. Thus, neutrophil numbers might be reduced in those with underlying inflammatory or metabolic disparities and may explain differences in healthy older individuals [11,15].

Although neutrophil numbers are associated with poor disease prognosis, their function is critical to their response. Neutrophil function is a difficult mechanism to assess in large scale studies due to their short half-life and inherent activation capacity. This is further augmented by the acute effects of exercise, which promotes a transient increase in cell numbers following acute exercise and the delay before returning to basal levels. Thus exercise studies are complicated by when and how to assess neutrophil function and to-date it remains unclear the ideal time that should be used.

Subsequently, few studies have assessed neutrophil function in response to exercise or physical activity. When compared to age-matched individuals completing 5000 steps/day, physical activity of over 10,000 steps/day was associated with better neutrophil chemotaxis towards the inflammatory chemokine IL-8 [11]. No differences were observed for phagocytic capacity or reactive oxygen species (ROS) production towards ingested E. coli, which is in contrast to other reports [10,16]. In these studies, increased physical activity in older individuals was associated with better phagocytic capacity than age matched physically inactive elders [10, 16]. In younger individuals, neutrophil chemotaxis, mitochondrial function and phagocytosis have all been improved either by an acute exercise bout or months of aerobic training [17, 18]. However, ROS production has been shown to be impaired during periods of excessive exercise training [19].

In older people with disease, the role of exercise on neutrophil function is even more complicated. Interpretation of results is difficult because it is unclear their pathogenic role. For example, in respiratory diseases such as COPD neutrophil function may be elevated or reduced and still contribute to disease pathology [20]. Twelve weeks of moderate-intensity walking was recently shown to reduce basal levels of ROS production and increase CD62L expression, suggesting an improved inflammatory and immune-surveillance phenotype in older individuals [21]. However, aquatic exercise for 8-months was associated with no improvements in phagocytic or che- motactic properties of neutrophils in women with fibromyalgia [22].

The release of extracellular DNA by neutrophils (NETs) as a mechanism of infection and tissue damage control has received significant attention recently. Although cell free DNA is associated with a number of inflammatory and disease conditions, NET production is reduced in healthy elders [23]. As NET production is associated with ROS activity and ROS activity is also reduced this would seem causally linked. However, elevated and uncontrolled NET production is associated with contributing to cell free DNA and thus disease such as atherosclerosis [24].

An interesting study by Beiter and colleagues suggested that NET release was increased following acute exercise [25]. They suggest that this response in a sterile, non-inflammatory state promotes immune homeostasis and protection from chronic inflammation through cross-talk with other immune cells such as dendritic and T-cells [25].

Taken together, exercise and physical activity has the potential to modify neutrophil cell composition and function in older adults. More work is required to fully understand the effects of exercise on neutrophil functions such as chemotaxis and microbicidal activity in seniors and whether there is relationship with overall improved health outcomes. Furthermore, little is known about the intensity, duration and type of exercise which can provide benefits to neutrophil function. Considering neutrophil function is severely impaired with age and is associated with the pathogenesis of many age-associated diseases it is perplexing that so little is known.

 
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