The open window theory indicates altered immunity 3 to 72 hours after exercise. The J-curve describes the risk of illness in response to exercise. The aim of this study was to examine the secretion of proinflammatory and anti-inflammatory cytokines before and after long-term strenuous exercise. Fourteen marathon and 16 half-marathon runners and 10 military cadets participating in a military ranger-training course were recruited to this study. Within-subject design was used measuring levels of plasma cytokines before, during, and after exercise. Plasma cytokines were measured using Luminex multiplex technology and ELISA. Comparing pre/post plasma levels both the marathon- and the half-marathon runners showed heavily increased levels of IL-6, IL-10, and IL-8 (P < 0.001). LPS stimulation among the half-marathon runners decreased the postrace levels of IL-6, IL-1b, and TNFα by 45%, 24%, and 43%, respectively (P < 0.01). During the ranger training course the spontaneous and LPS-stimulated levels of IL-6, IL-8, IL-10, IL-1b, and TNFα changed in a similar fashion as in the half-marathon runners although the fluctuations were smaller. Our study supports the open window and the J-curve theory; the immune system is more activated and the subjects are more threatened to infectious pathogens after intensive physical activity and in the period after exercise.

The present results indicate an exhaustion of leukocyte ROS-generating mechanisms after prolonged strenuous exercise. This may partly explain the observation that athletes are more sensitive to attract infectious diseases if exposed to pathogenic micro-organisms during the immediate period after intensive physical activity.

There still exist many unanswered questions whether physical exercise is beneficial or harmful to the immune system. The 'open-window' post-exercise hypothesis states that athletes are more susceptible to infections after exercise, but there is a need for further elucidation. The aim of the present study was to investigate the effect of long-distance running on leucocyte expression of selected adhesion molecules as well as the plasma levels of soluble leucocyte-and endotheliumderived adhesion molecules. Twenty-seven men participating in Oslo marathon together with 16 entrants (eight men and eight women) in the Oslo half-marathon were recruited to this study. Venous blood was collected before and immediately after the races for analysing the leucocyte expression of CD62L, CD11b and CD14 with the help of flow cytometry, and plasma concentrations of soluble (s) sE-selectin, sL-selectin, sP-selectin, sVCAM-1, sICAM-1 and sCD14 were assessed by means of enzyme-linked immunosorbent assays. A significant increase of leucocyte CD11b expression was observed following both races, compared to the pre-race situation. Monocyte CD14 expression increased only after the marathon race. After both races, CD62L expression was significantly lowered on all leucocyte subsets, whereas the plasma levels of sE-selectin, sP-selectin, sL-selectin, sVCAM-1, sICAM-1 and sCD14 were all increased. Altogether, these changes negatively influence the ability of leucocytes to adhere to and actively transmigrate the endothelium to reach the tissues. Our study thus supports the 'open-window' hypothesis, indicating a reduced capacity to combat infectious agents during the immediate post-exercise period.

Running leads to biochemical and hematological changes consistent with an inflammatory reaction to tissue injury. We report changes in the plasma concentration of the leukocyte-derived protein calprotectin after long-distance running. Blood samples were collected from runners before and after a marathon, half-marathon, a 30-km cross-country run, a military ranger-training course and short-term maximal physical exercise until exhaustion, VO2max. Leukocyte counts, plasma calprotectin concentration and calprotectin per neutrophilic granulocyte were assayed using a new method. During the marathon, half-marathon, the 30-km run, the ranger-training course and the VO2max exercise, calprotectin levels increased 96.3-fold, 13.3-fold, 20.1-fold, 7.5-fold and 3.4-fold, respectively. These changes may reflect damage to the tissues or vascular endothelium, causing microthrombi with subsequent activation of neutrophils. These cells are known to phagocytose platelets in microthrombi and may contribute to the prevention of clinical thrombosis. The half-life of calprotectin in plasma was about 5 h. The content of calprotectin per neutrophil remained unchanged during exercise at a level similar to that in healthy blood donors: mean: 25 pg/cell, range 18.8-33.6. A reference interval (mean +/- 2 SD) of 18.6-31.4 pg/cell is suggested.

We observed no influence of 4 weeks of dietary antioxidant supplementation on oxidative stress status. Based on these findings, there is no rationale advising athletes to ingest antioxidant supplements in addition to their regular diet if that includes daily recommended doses of vitamins.