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.