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.