An intense physical exercise induces an inflammatory reaction as demonstrated by the delayed increase in blood of acute phase proteins and among them of C-reactive protein (CRP). There is also evidence for a diminished acute phase reaction due to regular exercise suggesting a suppression of the inflammatory response through training. With this background CRP was measured by a sensitive enzyme immunoassay under resting conditions before and after 9 months of training in 14 subjects preparing for a marathon with the aim of studying the effect of training on the base-line CRP concentration. The mean distance run per week increased significantly from 31 +/- 9 km at the beginning to 53 +/- 15 km after 8 months of training (p < 0.01). The aerobic capacity rose significantly after training as demonstrated by the increase of running velocity during a maximal treadmill test from 3.82 +/- 0.29 m/s pre-training to 4.17 +/- 0.17 m/s post-training at a blood lactate concentration of 4 mmol/L (p< 0.01). In 10 of 12 runners base-line CRP was diminished after training in spite of a continuous increase of training intensity. The CRP median fell from 1.19 mg/L before to 0.82 mg/L after training (p < 0.05). Since intense physical exercise is known to be associated with an inflammatory reaction of muscles and tendons, the CRP decrease was unexpected. In 2 subjects the CRP concentration rose markedly because of a borrelia infection and a knee injury, respectively. These values were caused by a pathological condition and were not considered for the statistical evaluation. In 10 non-training control subjects the CRP median did not change significantly during the same 9 months period. The decrease of the CRP base-line concentration after training suggests that intensive regular exercise has a systemic anti-inflammatory effect. This is of particular interest with regard to several recent reports confering on the concentration of CRP in plasma a predictive value for the risk of cardiac infarction, venous thrombosis or stroke.

Serum ferritin, transferrin, haptoglobin, and iron were measured in well-trained middle- and long-distance runners, elite rowers of the West German national team, and professional racing cyclists during the summer training and the winter rest period. None of the male athletes examined, with the exception of the racing cyclists during the summer period, received oral or parenteral iron. The runners were found to have significantly lower ferritin (P less than 0.00001), iron (P less than 0.001), and haptoglobin values (P less than 0.01) than the controls. Their transferrin levels were elevated, however not significantly. Rowers showed significantly higher ferritin levels (P less than 0.01) than the controls. The reduced haptoglobin concentrations in runners are presumed to be caused by a running-induced hemolysis. It is speculated that a recurring hemoglobinuria produced diminished iron reserves in middle- and long-distance runners.

The effects of a 2.5-h running test on the plasma concentrations of elastase-alpha 1-antitrypsin, neopterin, tumor necrosis factor, and soluble interleukin-2 receptor were evaluated in eight healthy young male subjects. Neopterin was measured by radioimmunoassay, elastase-alpha 1-antitrypsin, tumor necrosis factor, and soluble interleukin-2 receptor by enzyme immunoassay. The post-exercise values were corrected for plasma volume changes which were calculated from hematocrit and hemoglobin values. Compared with the concentrations before exercise, elastase-alpha 1-antitrypsin values were significantly increased during the run (1 h after the start) (P less than 0.01) as well as during the first few hours after the end of the running test (P less than 0.01). A significant increase of tumor necrosis factor and neopterin was observed 1 h after the end and 1,3, and 24 h after the end of the running test, respectively, (P less than 0.01), and soluble interleukin-2 receptor concentrations were significantly elevated 1 and 2 days after exercise (P less than 0.01). The increase of elastase-alpha 1-antitrypsin, neopterin, tumor necrosis factor, and soluble interleukin-2 receptor supports the concept of a functional involvement of polymorphonuclear neutrophils and an activation of macrophages and T-lymphocytes after prolonged exercise.

In 11 healthy young subjects, the plasma concentrations of the thrombin-antithrombin III complex, fibrinopeptide A, tissue-plasminogen activator, complement fragments C3a and C4a, and histamine were measured before and after a graded maximal bicycle exercise test. The analyses were carried out 30 min before and immediately before exercise, immediately after exercise, and 30 and 60 min later. All post-exercise values were corrected for plasma volume changes, which were calculated from hematocrit and hemoglobin values. Immediately post-exercise, thrombin-antithrombin III, tissue-plasminogen activator, complement fragments C3a and C4a, and histamine were all significantly elevated (p less than 0.01), compared with the pre-exercise values; 30 and 60 min later the values normalized and significant differences from the pre-exercise values could no longer be measured. Fibrinopeptide A did not change significantly after exercise. The present results provide evidence for a simultaneous activation of coagulation, fibrinolysis, and complement system as well as for a release of histamine after a short maximal exercise.

Eight male subjects (mean age 24.1 +/- 2.6 years) performed at intervals of 2 weeks successively a 3 h and two 2 h runs of different running speed. The days following the running there were moderate elevations of C-reactive protein, haptoglobin, alpha-1-acid glycoprotein, coeruloplasmin, transferrin, alpha-1-antitrypsin and plasminogen. There were small or no changes of albumin, alpha-2-macroglobulin and hemopexin. The elevations of the "acute phase reactants" were examined in three male subjects following a 2 h run before and after an endurance training period of 9 weeks. This demonstrated a decreased acute phase response after training as illustrated by the changes of C-reactive protein, haptoglobin and alpha-1-acid glycoprotein in spite of higher posttraining running speeds. Well-trained athletes have elevated levels of the serum protease inhibitors alpha-1-antitrypsin, alpha-2-macroglobulin and C1-inhibitor. These antiproteolytic glycoproteins might limit exercise-induced inflammatory reactions.