Introduction
Inflammatory bowel disease (IBD) is a chronic active inflammatory
condition of the digestive tract. It includes both Crohn’s disease,
which can affect all parts of the digestive system, and ulcerative
colitis, which mainly affects the colon and rectum(1). IBD is caused by
an imbalance in the three major components that contribute to gut
homeostasis: the tissue, intestinal microbes, and immune cells(2,3).
During intestinal inflammation, intestinal cells, monocyte-derived
macrophages and T helper 17 cells stimulate the recruitment of
polymorphonuclear leukocytes (PMN) and monocytes through production of
chemokines and cytokines(2,4,5). The resulting gradients of these
mediators stimulate massive amounts of blood PMNs and monocytes to
transverse the endothelium and reach the lamina propria of the
intestinal tract, where PMNs and monocytes contribute to the
inflammation(2,6,7).
Exercise has a beneficial effect on IBD, likely by changing the three
major components that contribute to gut homeostasis (epithelium,
intestinal microbes, and immune cells) (8–10). A large observational
study showed that patients with stable IBD were significantly less
likely to develop active disease in six months when undertaking
activities(11). However, the underlying pathophysiologic mechanisms have
not been elucidated.
Several studies have shown an altered cellular adaptive immune response
(T-cell changes, Natural killer cell activity, salivary IgA production),
cytokine production (IL6, IL8, IL10) and innate immune responses
(granulocyte cell count, granulocyte respiratory burst,
neutrophil/lymphocyte ratio and macrophage activity) for several hours
to days, during recovery from prolonged exercise(12–15). However,
repeated bouts of prolonged moderate exercise result in acute
inflammation the first day, followed by a normalization/adaptation of
the immune response every consecutive day(15).
PMNs and monocytes play a critical role in the pathophysiology of
IBD(2,16,17). Responsiveness of PMNs and monocytes can be tested byin vitro, adding the bacterial/mitochondrial stimulus
N-Formylmethionine-leucyl-phenylalanine (fMLF)(18–20). Testing the
responsiveness of innate immune cells to fMLF is valuable to the
understanding of functional cellular activity in several
diseases(21–23). It is known that cellular responsiveness to fMLF is
significantly increased in patients with IBD flare-ups(24). Testing PMN
and monocyte responsiveness to fMLF might help in understanding the role
of PMNs and monocytes in exercise immunology. Therefore, the aim of this
study was to compare the responsiveness of these innate immune cells
after repeated bouts of prolonged
exercise in IBD patients and controls.