戸塚 学

An intensive training performed by athletes causes accumulation of physical fatigues, which leads to immunity depression and overtraining syndrome. Especially in endurance sports, physical fatigue tends to accumulate as it takes time to recover from physical conditions after the race or intensive training. In this study, we have investigated the conditions of marathon runners after one week of Ekiden （relay road race） according to the levels of muscle enzymes and serum opsonic activity （SOA）. Subjects were 28 top male runners in Japanese University Ekiden. Out of all 28 subjects, 11 of them who had a race before a week of investigation were considered as the race group, and the rest were considered as the control group. Although no significant difference were found in running distance and duration of training among the two groups, muscular enzyme levels were significantly high （p<0.05）,and SOA levels of LgCL, PH and AUC tended to be higher in the race group than the control group. This showed the higher damage of the muscle, and a possibility that it may have reflected the increase in ROS production in the race group compared to the control group. In conclusion, there was a possibility that the endurance of athletes were not fully recovered from the muscle fatigue causing increase of ROS production even after a week of the race. Therefore,long-distance runners were suggested to carry out a reduced amount of less-intense, less-frequent training with sufficient rests at least for a week after a race competition.

近年，適度な運動が酸化ストレスを減少させることが報告されている．しかし，そのメカニズムについてはいまだ明らかにされていない．本研究では，酸化ストレスの原因となる好中球の活性酸素種 (ROS) 産生量に週１回， ６ヵ月間の健康実践教室（運動教室と栄養教室）が及ぼす影響について調査した．対象は，岩木健康増進プロジェクトの平成20年度健康実践教室に参加した29名である．この教室の前，中間，後に体組成測定，血液検査，好中球ROS産生を反映する血清オプソニン化活性を測定した．その結果，教室後に体脂肪率，血圧，総コレステロールの低下，HDLコレステロールの上昇がみられ，さらに血清オプソニン化活性も低下していた．すなわち，教室参加は肥満や生活習慣病関連項目を改善させるとともに，酸化ストレスの原因である好中球由来ROSを抑制した可能性が考えられた．

成長期の子どもの身体組成及び体力と生活状況との関連について同一被験者により小学6年次と中学2年次について比較検討した。男女ともに小学6年次から中学2年次にかけて身長〜体重とともに増加した。また、BMIも増加した。身体組成は、男子の体脂肪率を除いては除脂肪体重、骨密度において有意な増加が示された。小学校から中学校にかけて呼吸循環機能の発達により全身持久性能力が著しい伸びを示すことが確認された。小学6年次では、男子は運動時間と除脂肪体重を除く身体組成の指標、女子では運動時間と握力・長座体前屈を除く体力指標との間に関連が見られた。中学2年次では、男子では、上体起こし、立ち幅跳びといった体力指標との間で関連がみられるようになった。女子では、運動時間と体力指標との関連性は、上体起こしを除いては認めなくなった。そして、新たに睡眠時間と体脂肪率との間に関連性を認めた。

In order to examine in detail the influence on the neutrophil immune function in sumo wrestlers of performing traditional and original training we examined changes in the neutrophil immune function in 17 male amateur university sumo wrestlers (aged 20.2 +/- 1.5 years), before ('Pre') and after the training ('Post') for 2.5 h under fasting conditions. Assays included blood leukocyte and neutrophil counts, serum concentration of immunoglobulins, complements, myogenic enzymes and neutrophil oxidative burst activity (OBA) and phagocytic activity (PA). Myogenic enzymes, neutrophil counts, the ratio of neutrophil counts:leukocyte counts significantly increased and immunoglobulins and complements decreased in Post compared with Pre. There was a positive correlation between the change of neutrophil counts before and after the training and the change of creatine kinase (r = 0.667, p &lt; 0.01). The Post OBA significantly increased and PA significantly decreased compared with Pre. It was concluded that sumo training causes muscular damage and an increase in the neutrophil count as a response. In this time, although OBA increased, PA decreased after training. Compensation between PA and reactive oxygen species production may exist to maintain the overall integrity of the neutrophil immune function. Copyright (C) 2008 John Wiley & Sons, Ltd.

The present study examined the effects of judo training on neutrophil and related functions. We measured and studied changes in the neutrophil and its related functions in 22 male university judoists immediately before (Pre values) and immediately after (Post values) a 2 h training session: reactive oxygen species (ROS) production capability, phagocytic activities (PA) and serum opsonic activity (SOA). Neutrophil count in whole blood, myogenic enzymes (creatine kinase, lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase), immunoglobulins (IgG, IgA and IgM) and complements (C3 and C4) in serum were also measured. The Post values of the neutrophil count, myogenic enzymes and IgG increased significantly compared with the Pre values. ROS production capability and SOA also significantly increased following training, although PA showed a slight decrease (but not statistically significant). Taking the findings of our previous studies into consideration, three major neutrophil or related functions, namely ROS production capability, PA and SOA, might compensate for each other to maintain the overall integrity of the neutrophil immune function, in that ROS and SOA increased to compensate for the slight decrease in PA, or PA slightly decreased to compensate for the increase in ROA and SOA after exercise. Copyright (c) 2008 John Wiley & Sons, Ltd.

Objective: The number of bedridden elderly patients who. need a liquid diet has been increasing. We, evaluated the usefulness of a tube-fed liquid diet containing cellulose and oligosaccharide for elderly bedridden patients. Methods: Twenty-two elderly bedridden patients were given a liquid diet containing cellulose and lafinose for 4 wk. Parameters associated with blood and stool weight were measured during this period. Results: Stool weight increased by 32.0 g in men and 8.8 g in women at 2 wk and remained at these weights up to 4 wk (P &lt; 0.05 before and after 2 wk, 3 wk, and 4. wk in men, and P &lt;0.05 before and after 3 wk in women). Body weight increased in men (0.5 kg) and women (0.7 kg) 15 d after starting the diet and then remained at these values up to 29 d thereafter, and statistically significant differences were not seen. There.were no changes in nutritional parameters such as total protein: Conclusion: No significant changes were observed in the general condition of elderly patients, with the exception of a positive increase in fecal weight,by 30-d. supplementation of a liquid diet containing cellulose and lafinose. (C) 2004 Elsevier Inc. All rights reserved.

In this study, we examined the effects of weight reduction by restricting energy intake on muscle function and serum concentrations of myogenic enzymes in judoists. Twenty-seven male judoists aged 19.3+/-0.6 years (mean+/- s ) were divided into three groups based on the extent of body weight reduction: high weight reduction (height 1.70+/-0.05 m, body mass 78.5 +/-13.6 kg), low weight reduction (height 1.70+/-0.05 m, body mass 80.7+/-13.1 kg) and a group that maintained body weight while continuing to perform exercise training (height 1.78+/- 0.07 m, body mass 78.7+/-8.8 kg). Body composition, blood biochemistry, energy intake and anaerobic power were assessed on four occasions: 20 days (baseline data), 4 days and 1 day before and 7 days after competition. Compared with baseline, body mass and fat-free mass were significantly lower 1 day before competition in the high and low weight reduction groups (both P &lt;0.01); these changes persisted for 7 days after competition in the high weight reduction group. Serum creatine kinase was significantly elevated 1 day before competition in all groups (all P &lt;0.05), and remained higher 7 days after competition in both the high and low weight reduction groups. Compared with baseline, maximal anaerobic power was significantly lower 1 day before competition only in the high weight reduction group ( P &lt;0.01). Our results suggest that energy restriction in addition to intense exercise training before major competition has an adverse effect on anaerobic power and elevates serum creatine kinase concentration, leading to an impairment of muscular function and an increased susceptibility of muscle tissue to injury.

It is known that interleukin (IL)-12 p70 promotes the differentiation of type-1 helper T (Th1) cells, which produce type-1 cytokines such as IL-2 and interferon (IFN), thereby supporting cellular immunity, whereas IL-12 p40 acts as an antagonist of IL-12 p70. In contrast, IL-4 and IL-6 promote the differentiation of Th2 cells, which produce type-2 cytokines IL-4, IL-6 and IL-10, induce humoral immunity and are involved in allergic reactions. Exhaustive exercise causes the suppression of T lymphocyte activity while asthmatic and allergic diseases are subclinically more prevalent in athletes. One of the mechanisms behind these observations might be a lower type-1 and higher type-2 cytokine balance, which we previously demonstrated to occur after exhaustive exercise. In the present study, we investigated the type-1/type-2 cytokine balance by measuring plasma concentrations of IL-2, IL-4, IL-5, IL-10, tumor necrosis factor (TNF)-alpha and IFN-gamma with microparticle-based flow cytometric technology. IL-5, IL-6 and IL-13 were measured by enzyme-linked immunosorbent assay (ELISA). IL-12 p40 and p70 were measured separately, also by ELISA. Plasma IL-12 p40 concentration rose significantly after maximal exercise and to an even greater extent after a marathon race. Conversely, plasma IL-12 p70 could not be detected even using two different assays. The marathon race caused a marked increase in the plasma concentrations of IL-6 and IL-10. Their responses were correlated (r=0.78, p&lt;0.01), indicating that IL-6 is an inducer of IL-10, and may partly induce the type-1 &lt; type-2 cytokine balance. With the exception of one study involving maximal exercise, other studies have failed to show any change in circulating IL-12 concentration with exercise. The present study demonstrated that IL-12 p40 was present in excess of p70 especially after exercise. This may be one of the mechanisms behind several phenomena including cellular immunosuppression, an increase in the relative proportion of type-2 cytokines following exhaustive exercise, and the higher incidence of infections and allergic disorders in regularly exercising endurance athletes.

It is known that interleukin (IL)-12 p70 promotes the differentiation of type-1 helper T (Th1) cells, which produce type-1 cytokines such as IL-2 and interferon (IFN), thereby supporting cellular immunity, whereas IL-12 p40 acts as an antagonist of IL-12 p70. In contrast, IL-4 and IL-6 promote the differentiation of Th2 cells, which produce type-2 cytokines IL-4, IL-6 and IL-10, induce humoral immunity and are involved in allergic reactions. Exhaustive exercise causes the suppression of T lymphocyte activity while asthmatic and allergic diseases are subclinically more prevalent in athletes. One of the mechanisms behind these observations might be a lower type-1 and higher type-2 cytokine balance, which we previously demonstrated to occur after exhaustive exercise. In the present study, we investigated the type-1/type-2 cytokine balance by measuring plasma concentrations of IL-2, IL-4, IL-5, IL-10, tumor necrosis factor (TNF)-alpha and IFN-gamma with microparticle-based flow cytometric technology. IL-5, IL-6 and IL-13 were measured by enzyme-linked immunosorbent assay (ELISA). IL-12 p40 and p70 were measured separately, also by ELISA. Plasma IL-12 p40 concentration rose significantly after maximal exercise and to an even greater extent after a marathon race. Conversely, plasma IL-12 p70 could not be detected even using two different assays. The marathon race caused a marked increase in the plasma concentrations of IL-6 and IL-10. Their responses were correlated (r=0.78, p&lt;0.01), indicating that IL-6 is an inducer of IL-10, and may partly induce the type-1 &lt; type-2 cytokine balance. With the exception of one study involving maximal exercise, other studies have failed to show any change in circulating IL-12 concentration with exercise. The present study demonstrated that IL-12 p40 was present in excess of p70 especially after exercise. This may be one of the mechanisms behind several phenomena including cellular immunosuppression, an increase in the relative proportion of type-2 cytokines following exhaustive exercise, and the higher incidence of infections and allergic disorders in regularly exercising endurance athletes.

We investigated whether there is a break point of creatine kinase (CK) release after daily endurance exercise and whether CK response depends on individual physical characteristics. Fifteen healthy young men performed 90 min of bicycle exercise for 3 consecutive days. Body composition, properties of the quadriceps femoris muscle (QFM), and aerobic and anaerobic capacities were estimated before the test. Blood samples were obtained 22 times during the experimental period. Endurance exercise significantly elevated serum CK from 3 h after the first exercise session (P &lt; 0.05) and gradually increased thereafter. Subjects were classified into two groups according to their peak CK values: high responders (HR; &gt;500 IU/l of CK) and low responders (LR; &lt;300 IU/l of CK). Peak CK values during the experimental period correlated (P &lt; 0.01) with workload/cross-sectional area of the QFM (r = 0.658), workload/volume of the QFM (r = 0.648), and knee extensor strength/body mass (r = -0.634); however, the HR and LR groups were separated in each variable. Thus the break point of CK release after endurance exercise under these conditions is 300-500 IU/l, two or three times higher than in the resting condition, and is associated with properties of the QFM.

We investigated whether there is a break point of creatine kinase (CK) release after daily endurance exercise and whether CK response depends on individual physical characteristics. Fifteen healthy young men performed 90 min of bicycle exercise for 3 consecutive days. Body composition, properties of the quadriceps femoris muscle (QFM), and aerobic and anaerobic capacities were estimated before the test. Blood samples were obtained 22 times during the experimental period. Endurance exercise significantly elevated serum CK from 3 h after the first exercise session (P &lt; 0.05) and gradually increased thereafter. Subjects were classified into two groups according to their peak CK values: high responders (HR; &gt;500 IU/l of CK) and low responders (LR; &lt;300 IU/l of CK). Peak CK values during the experimental period correlated (P &lt; 0.01) with workload/cross-sectional area of the QFM (r = 0.658), workload/volume of the QFM (r = 0.648), and knee extensor strength/body mass (r = -0.634); however, the HR and LR groups were separated in each variable. Thus the break point of CK release after endurance exercise under these conditions is 300-500 IU/l, two or three times higher than in the resting condition, and is associated with properties of the QFM.

We studied changes in serum opsonic activity (SOA) in male judoists who were engaged in active weight reduction. Serum immunoglobulins, complements and SOA, measured by neutrophil-associated chemiluminescence responses. were investigated 20 days, 7 days and I day before a competition and 5 days after the competition, In addition, muscle strength and anaerobic work capacity, as well as body composition, were also determined. A dietary survey was conducted daily during the observation period, Body weight decreased by 4.2 kg over 19 days. SOA significantly decreased 5 days alter the competition. as well as the concentrations of serum immunoglobulins. complements and total proteins. These trends were noted in the marked weight reduction group (i.e. reduction weight of body fat/body fat weight before weight reduction greater than or equal to25%() more than the slight reduction group (&lt;25%). Depressed SOA was closely correlated with the decreased concentrations of intmunoglobulins and complements. These results suggest that the decrease in immunoglobulins and complements following weight reduction is associated with reduced SOA, which might cause susceptibility to infections. This study demonstrated that such immunosuppression appeared in the recovery period after the competition rather than immediately before the competition. Copyright (C) 2002 John Wiley Sons. Ltd.

We studied changes in serum opsonic activity (SOA) in male judoists who were engaged in active weight reduction. Serum immunoglobulins, complements and SOA, measured by neutrophil-associated chemiluminescence responses. were investigated 20 days, 7 days and I day before a competition and 5 days after the competition, In addition, muscle strength and anaerobic work capacity, as well as body composition, were also determined. A dietary survey was conducted daily during the observation period, Body weight decreased by 4.2 kg over 19 days. SOA significantly decreased 5 days alter the competition. as well as the concentrations of serum immunoglobulins. complements and total proteins. These trends were noted in the marked weight reduction group (i.e. reduction weight of body fat/body fat weight before weight reduction greater than or equal to25%() more than the slight reduction group (&lt;25%). Depressed SOA was closely correlated with the decreased concentrations of intmunoglobulins and complements. These results suggest that the decrease in immunoglobulins and complements following weight reduction is associated with reduced SOA, which might cause susceptibility to infections. This study demonstrated that such immunosuppression appeared in the recovery period after the competition rather than immediately before the competition. Copyright (C) 2002 John Wiley Sons. Ltd.

We examined the hypothesis that the short, intensive exercise-induced increase in circulating neutrophil counts is affected by the interaction between the endocrine and immune systems. Twelve male winter-sports athletes underwent a maximal exercise test on a treadmill. Blood samples were collected before, immediately after (Post), and 1 h (Post 1 h) and 2 h (Post 2 h) after the exercise. The neutrophil counts increased significantly at Post 1 h (P &lt; 0.05) and remained significantly high even at Post 2 h (P &lt; 0.05), showing a leftward shift. Plasma granulocyte colony-stimulating factor (G-CSF) increased at Post (P &lt; 0.05), and interleukin-6 (IL-6) increased at Post 1 h (P &lt; 0.05). Plasma G-CSF at Post significantly correlated with the numbers of both neutrophils and stab cells at Post 1 h (P &lt; 0.05). Plasma IL-6 at Post 1 h levels also correlated significantly with the number of neutrophils at Post 2 h (P &lt; 0.05). The increase in the levels of plasma G-CSF and IL-6 after intensive exercise may play a role in the mobilization of neutrophils into the circulatory system.

We examined the hypothesis that the short, intensive exercise-induced increase in circulating neutrophil counts is affected by the interaction between the endocrine and immune systems. Twelve male winter-sports athletes underwent a maximal exercise test on a treadmill. Blood samples were collected before, immediately after (Post), and 1 h (Post 1 h) and 2 h (Post 2 h) after the exercise. The neutrophil counts increased significantly at Post 1 h (P &lt; 0.05) and remained significantly high even at Post 2 h (P &lt; 0.05), showing a leftward shift. Plasma granulocyte colony-stimulating factor (G-CSF) increased at Post (P &lt; 0.05), and interleukin-6 (IL-6) increased at Post 1 h (P &lt; 0.05). Plasma G-CSF at Post significantly correlated with the numbers of both neutrophils and stab cells at Post 1 h (P &lt; 0.05). Plasma IL-6 at Post 1 h levels also correlated significantly with the number of neutrophils at Post 2 h (P &lt; 0.05). The increase in the levels of plasma G-CSF and IL-6 after intensive exercise may play a role in the mobilization of neutrophils into the circulatory system.

We studied changes in serum opsonic activity (SOA) in male judoists who were engaged in active weight reduction. Serum immunoglobulins, complements and SOA, measured by neutrophil-associated chemiluminescence responses. were investigated 20 days, 7 days and I day before a competition and 5 days after the competition, In addition, muscle strength and anaerobic work capacity, as well as body composition, were also determined. A dietary survey was conducted daily during the observation period, Body weight decreased by 4.2 kg over 19 days. SOA significantly decreased 5 days alter the competition. as well as the concentrations of serum immunoglobulins. complements and total proteins. These trends were noted in the marked weight reduction group (i.e. reduction weight of body fat/body fat weight before weight reduction greater than or equal to25%() more than the slight reduction group (&lt;25%). Depressed SOA was closely correlated with the decreased concentrations of intmunoglobulins and complements. These results suggest that the decrease in immunoglobulins and complements following weight reduction is associated with reduced SOA, which might cause susceptibility to infections. This study demonstrated that such immunosuppression appeared in the recovery period after the competition rather than immediately before the competition. Copyright (C) 2002 John Wiley Sons. Ltd.

It has been documented that strenuous exercise not only induces pyrogenesis but also elicits mobilization and functional augmentation of neutrophils and monocytes whereas it suppresses cellular immunity leading to increased susceptibility to infections. As mediators Of these phenomena, cytokines released into the circulation have been a recent focus of attention. Indeed, there are as many as one hundred original reports concerning exercise and cytokines, and half of them have been published in rapid succession from 2000, resulting in a tremendous accumulation of new knowledge within such a short term. The first aim of this review is to comprehensively summarize previous studies on systemic cytokine kinetics following exercise, with a special focus on reproducibility and quantitative comparison in human studies using specific immunoassays. Although tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 beta have traditionally been understood to be the main inducer cytokines of acute phase reactions, the majority of studies have shown that the circulating concentration of these cytokines is either unchanged following exercise, or exhibits relatively small, delayed increments. Plasma interferon (IFN)-alpha and IFN-gamma do not appear to change following exercise, whereas IL-2 decreases after endurance exercise. The small changes of these proinflammatory and immunomodulatory cytokines could well be mediated by anti-inflammatory cytokines such as IL-1 receptor antagonist (IL-1ra), IL-6 and IL-10 and cytokine inhibitors (cortisol, prostaglandin E-2 and soluble receptors against TNF and IL-2), which are known to increase markedly in the circulation following endurance exercise. Moreover it has been recently demonstrated that endurance exercise induces systemic release of granulocyte colony-stimulating factor (G-CSF), macrophage CSF (M-CSF), IL-8 and monocyte chemotactic protein 1 (MCP-1). Although the majority of available data have been obtained following prolonged exercise, it remains to be elucidated whether short-duration intensive exercise also causes rapid systemic cytokine release. In addition, there have been few studies that have simultaneously compared the extent of each cytokine response to exercise from a wider perspective. The second aim of this study was to examine possible changes of not only plasma but also urine concentrations of a broad spectrum of cytokines (16 kinds) following maximal exercise, including the time course of recovery. Although plasma TNF-alpha could not be detected throughout, it was present in urine 2 It after exercise. Plasma IL-1 beta rose significantly 2 h after exercise, but plasma IL-1ra increased more rapidly and markedly than IL-1 beta, thus IL-1 bioactivity should be blocked at least in the circulation. Although there was only a trend toward increased plasma IL-6 concentrations after exercise, urine IL-6 rose significantly I h after exercise, indicating that IL-6 was released systemically but eliminated rapidly into the urine. Furthermore, it is shown for the first time that plasma and urine IL-4 concentrations were significantly elevated 2 h after exercise. Therefore, it is possible that anti-inflammatory cytokines might be released into the circulation as a regulatory mode of the cytokine network for adaptation against systemic inflammatory stress. Additionally, we have demonstrated that plasma concentrations of G-CSF granulocyte-macrophage CSF (GM-CSF), M-CSF IL-8 and MCP-1 increased immediately after short-duration exercise and that the urine concentrations of these cytokines were much more pronounced than the changes observed in plasma. In conclusion, cytokines that are considered to induce systemic bioactivity following exercise are not only anti-inflammatory cytokines but also colony-stimulating factors and chemokines, which were secreted in an earlier phase of exercise without the kinetic involvement of traditional proinflammatory cytokines. Although the wider physiological and pathological implications are still not clearly understood, these cytokine kinetics may partly explain suppressed cell-mediated immunity and increased allergic reactions derived from a lower type-1 to type-2 cytokine ratio, along with mobilization and functional augmentation of neutrophils and monocytes. The sources and stimuli of cytokine production are not fully elucidated at present, but several hypotheses based on recent experimental evidence are discussed in this review herein.

It has been documented that strenuous exercise not only induces pyrogenesis but also elicits mobilization and functional augmentation of neutrophils and monocytes whereas it suppresses cellular immunity leading to increased susceptibility to infections. As mediators Of these phenomena, cytokines released into the circulation have been a recent focus of attention. Indeed, there are as many as one hundred original reports concerning exercise and cytokines, and half of them have been published in rapid succession from 2000, resulting in a tremendous accumulation of new knowledge within such a short term. The first aim of this review is to comprehensively summarize previous studies on systemic cytokine kinetics following exercise, with a special focus on reproducibility and quantitative comparison in human studies using specific immunoassays. Although tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 beta have traditionally been understood to be the main inducer cytokines of acute phase reactions, the majority of studies have shown that the circulating concentration of these cytokines is either unchanged following exercise, or exhibits relatively small, delayed increments. Plasma interferon (IFN)-alpha and IFN-gamma do not appear to change following exercise, whereas IL-2 decreases after endurance exercise. The small changes of these proinflammatory and immunomodulatory cytokines could well be mediated by anti-inflammatory cytokines such as IL-1 receptor antagonist (IL-1ra), IL-6 and IL-10 and cytokine inhibitors (cortisol, prostaglandin E-2 and soluble receptors against TNF and IL-2), which are known to increase markedly in the circulation following endurance exercise. Moreover it has been recently demonstrated that endurance exercise induces systemic release of granulocyte colony-stimulating factor (G-CSF), macrophage CSF (M-CSF), IL-8 and monocyte chemotactic protein 1 (MCP-1). Although the majority of available data have been obtained following prolonged exercise, it remains to be elucidated whether short-duration intensive exercise also causes rapid systemic cytokine release. In addition, there have been few studies that have simultaneously compared the extent of each cytokine response to exercise from a wider perspective. The second aim of this study was to examine possible changes of not only plasma but also urine concentrations of a broad spectrum of cytokines (16 kinds) following maximal exercise, including the time course of recovery. Although plasma TNF-alpha could not be detected throughout, it was present in urine 2 It after exercise. Plasma IL-1 beta rose significantly 2 h after exercise, but plasma IL-1ra increased more rapidly and markedly than IL-1 beta, thus IL-1 bioactivity should be blocked at least in the circulation. Although there was only a trend toward increased plasma IL-6 concentrations after exercise, urine IL-6 rose significantly I h after exercise, indicating that IL-6 was released systemically but eliminated rapidly into the urine. Furthermore, it is shown for the first time that plasma and urine IL-4 concentrations were significantly elevated 2 h after exercise. Therefore, it is possible that anti-inflammatory cytokines might be released into the circulation as a regulatory mode of the cytokine network for adaptation against systemic inflammatory stress. Additionally, we have demonstrated that plasma concentrations of G-CSF granulocyte-macrophage CSF (GM-CSF), M-CSF IL-8 and MCP-1 increased immediately after short-duration exercise and that the urine concentrations of these cytokines were much more pronounced than the changes observed in plasma. In conclusion, cytokines that are considered to induce systemic bioactivity following exercise are not only anti-inflammatory cytokines but also colony-stimulating factors and chemokines, which were secreted in an earlier phase of exercise without the kinetic involvement of traditional proinflammatory cytokines. Although the wider physiological and pathological implications are still not clearly understood, these cytokine kinetics may partly explain suppressed cell-mediated immunity and increased allergic reactions derived from a lower type-1 to type-2 cytokine ratio, along with mobilization and functional augmentation of neutrophils and monocytes. The sources and stimuli of cytokine production are not fully elucidated at present, but several hypotheses based on recent experimental evidence are discussed in this review herein.