Discussion
This study investigated the effect of 3 repeated bouts of prolonged exercise on neutrophils, eosinophils and monocytes in patients with inflammatory bowel disease. We used automated point-of-care flow cytometry in a field laboratory with an integrated system to test the fMLF responsiveness of eosinophils, neutrophils and monocytes. We found that IBD patients demonstrated a smaller increase in neutrophil and monocyte responsiveness in activation markers CD35 and CD11b towards an inflammatory stimulus after repeated walking, compared to non-IBD walkers. A decreased neutrophil responsiveness was also observed in the activation/maturation marker CD10.
In previous studies on repeated prolonged exercise, conducted during the same walking event, a general increase in cytokines and direct innate immune activation was found after the first day in all tested participants(15). After the second and third day a normalization/adaptation of the innate immune system was demonstrated. The present study showed no difference between controls and IBD patients in responsiveness of neutrophils, eosinophils and monocytes to fMLF during the first 2 days of exercise (results not shown). Only at day 3 increased responsiveness of neutrophil and monocytes was found in all walkers (IBD and non-IBD), but was significantly less increased in IBD patients pointing. The underlying mechanism remains to be established, but it is tempting to speculate that increased responsiveness is the result of a priming effect in response to damage-associated molecular patterns (DAMPs) originating from mild-exercise-induced tissue damage during the first 2 days. Apparently, this situation leads to a suppression of the proinflammatory response in IBD patients.
The neutrophil activation markers CD35, CD11b and CD10 showed the same significant differences between the study groups after 3 days of repeated bouts of prolonged exercise. The complement receptors CD11b and CD35 showed no difference in expression between participants with IBD and without IBD at day 0. However, CD10 was also significantly different at day 0, which might be an indirect effect of the additional role of maturation marker (28). Patients with IBD are characterized by chronic inflammation, which might associate to an overall younger neutrophil compartment (left shift) in the bloodstream(2).
In diseases with hypo inflammation of the innate immune system, a decreased neutrophil responsiveness in the peripheral blood is associated with worse clinical outcomes (infectious complications and sepsis)(22,23,29). In diseases associated with hyper inflammation, decreased neutrophil responsiveness is associated with better clinical outcomes (allergic/auto-immune diseases)(30). Three days of exercise in IBD patients is associated with the occurrence of less increased responsive neutrophils and monocytes in the peripheral blood. Possibly explaining the better clinical outcomes in IBD patients.
In conclusion, increased responsiveness of neutrophils and monocyte to fMLF was demonstrated after repetitive bouts of prolonged exercise. Interestingly, this exercise was associated with relative refractoriness of both neutrophils and monocytes in IBD patients. These refractory cells might create a lower inflammatory state in the intestine, providing a putative mechanism for the decrease in flare-ups in IBD patients after repeated exercise.