Shigeyoshi Kurakake

Circulating cytokines and hormones with immunosuppressive but neutrophil-priming potentials rise after endurance exercise in humans

Abstract To investigate the mechanisms of exercise-induced immune perturbations, we measured promising immunomodulatory hormones and cytokines in plasma of 16 male marathon runners before and after a competitive 42.195-km race. Interleukin 1-beta (IL-1β) and interferon gamma (IFN-γ) concentrations remained unchanged after the marathon. The cytokines IL-12, IFN-α and tumour necrosis factor alpha (TNF-α) could not be detected even using highly sensitive specific immunoassays, indicating at least that overshooting responses of these cytokines had not occurred after exercise. As mechanisms for the small changes in these cytokines, we demonstrated for the first time a significant rise in concentrations of inhibitory cytokine IL-10 in addition to the immunosuppressive hormone cortisol, although concentrations of IL-4 and transforming growth factor-beta (TGF-β) were unaffected by the race. Furthermore, concentrations of IL-1 receptor antagonist (IL-1ra) and IL-6, which are negative-feedback inhibitors of cytokine production, increased by more than 100 times. As for humoral mediators of neutrophil mobilization, concentrations of growth hormone (GH), cortisol and granulocyte colony-stimulating factor (G-CSF) increased significantly. In addition, concentrations of neutrophil-priming substances (IL-6, IL-8, G-CSF, GH and prolactin) also increased significantly and the induction of IL-8 and G-CSF with exercise was demonstrated for the first time in the present study. In contrast, IL-2 concentration decreased, by 32%, and this was correlated with the induction of nitric oxide (NO) production. Muscle damage, monitored using changes in concentrations of creatine kinase and myoglobin, was also observed. These results suggested that exercise-induced pathogenesis including previously reported immunosuppression and neutrophil hyper-reactivity might be attributed, at least partly, to the systemic dynamics of the above bioactive substances.

Impact of a competitive marathon race on systemic cytokine and neutrophil responses

PURPOSE To investigate whether cytokines and neutrophils mediate exercise-related pathogenesis, we examined their responses and possible association after exhaustive exercise. METHODS Plasma and urine samples were obtained from 10 male runners before and after a 42.195-km marathon race. Major cytokines and neutrophil activation markers [myeloperoxidase (MPO) and lactoferrin (LTF)] were measured by enzyme-linked immunosorbent assays. Functional modulation of standard neutrophils and monocytes by plasma was determined on their luminol-dependent chemiluminescence responses. RESULTS The race induced peripheral neutrophilia accompanied by an increase in band neutrophils and monocytosis. Plasma MPO and LTF concentrations increased significantly by 1.8 and 1.4 times after the race. There was a greater increase in urine concentrations of MPO and LTF, 12.3 and 3.5 times after exercise, respectively, suggesting that neutrophil activation occurred and that renal clearance exceeded the increase in plasma concentrations. Plasma interleukin (IL)-6, IL-8, IL-10, granulocyte colony-stimulating factor (G-CSF), macrophage CSF (M-CSF), and monocyte chemotactic protein 1 (MCP-1) increased significantly after the race, and urine IL-1beta, IL-6, G-CSF, M-CSF, and MCP-1 increased significantly. The plasma IL-6 responses correlated with the increases of band neutrophil count (r = 0.860, P < 0.01), suggesting IL-6-mediated bone marrow release of neutrophils. Furthermore, the increases in urine MPO concentration were correlated with increases in urine IL-6 (r = 0.868, P < 0.01) and G-CSF (r = 0.875, P < 0.01), suggesting that these cytokines promoted neutrophil activation. However, preincubation of neutrophils and monocytes with postexercise plasma could not cause priming responses, possibly because of the exercise-induced enhancement of plasma antioxidant activity. CONCLUSION Although many cytokines recruiting and priming neutrophils and monocytes were secreted and functional after exhaustive exercise, overwhelming antioxidant and antiinflammatory defenses were induced, preventing exercise-induced oxidative stress.

Changes in Physical Characteristics, Hematological Parameters and Nutrients and Food Intake during Weight Reduction in Judoists

We studied changes in physical characteristics: body composition; muscle and physical strength; hematological parameters; and nutrients and food intake in 22 male college judoists who were losing weight purposefully. Nutritional parameters in blood, such as triglycerides, decreased immediately before matches and rebounded after matches. Free fatty acid increased before matches and returned to previous levels 10 days after matches. IgM and complements decreased before matches and did not return to previous levels even 10 days after matches. These changes were noted in the marked weight reduction group (weight lost / body weight before weight reduction, weight reduction rate≥6%). In contrast, creatine kinase increased before matches in the slight and moderate weight reduction groups (weight reduction rate< 3%, 3≤and<6%, respectively). The marked weight reduction group showed no changes in creatine kinase, however, indicating inadequate exercise due to excessive weight reduction. Muscle strength (grip) and nutrients and food intake decreased significantly before matches. These changes were noted in the marked weight reduction group. These findings suggested that a weight reduction rate of 6% or more adversely affected the performance and health of the judoist.

A study for prevention of chronic fatigue. part 2. effects of strenuous physical exercise performed in a training camp on serum enzyme activity levels and subjective fatigue.

The principal objective of this paper is to develop a simple and rapid method of estimating levels of fatigue so that chronic fatigue can be prevented. Long-distance runners belonging to a successful corporate team (Group A; 25 males) and representative runners at the prefectural level (Group B; 14 males) participated in this study. We examined the effects of strenuous physical exercise on serum enzyme activity and the fatigue level felt by the runners (subjective fatigue).The following parameters were measured on two consecutive mornings during a training period: physical characteristics, serum-biochemistry using the dry-chemistry method, and subjective fatigue determined using the questionnaire regarding subjective symptoms authorized by the Japan Association of Industrial Health and the Profile of Mood State (POMS). Group A was divided into A-Senior (17 males; highest performance level) and A-Freshman (8 males) subgroups according to the length of employment within the corporation (one year or more and less than one year, respectively).The levels of serum aspartate aminotransferase (AST) and creatine kinase (CK) were significantly lower in the A-Senior group than the other groups and this group displayed the “iceberg” POMS profile at both examinations. Some significant correlations between the elements of POMS and serum enzyme activity levels were observed among all three groups during both examinations. The decline of serum CK levels tended to accompany a decrease in “Fatigue” according to POMS among 9 of 17 members of the A-Senior group. This tendency between the A-Senior and the A-Freshman groups statistically differed according to theX - square analysis.Our results suggest that the effects of physical stress on serum enzyme activity levels and subjective fatigue are affected by performance levels. Physical fatigue seemed to be reflected by serum CK levels. Monitoring subjective fatigue while measuring serum enzyme activity levels using the dry-chemistry method immediately provides clinical value to players and coaches on site, and should therefore help to prevent a shift from “overreaching” to “overtraining”.