***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: The fatigue induced by marathon races was observed in terms of inflammatory and immunological outcomes . Neutrophil survival and activation are essential for inflammation resolution and contributes directly to the pathogenesis of many infectious and inflammatory conditions . The aim of this study was to investigate the effect of marathon races on surface molecules related to neutrophil adhesion and extrinsic apoptosis pathway and its association with inflammatory markers . We evaluated 23 trained male runners at the São Paulo International Marathon 2013 . The following components were measured : hematological and inflammatory mediators , muscle damage markers , and neutrophil function . The marathon race induced an increased leukocyte and neutrophil counts ; creatine kinase ( CK ) , lactate dehydrogenase ( LDH ) , CK-MB , interleukin (IL)-6 , IL-10 , and IL-8 levels . C-reactive protein ( CRP ) , IL-12 , and tumor necrosis factor (TNF)-α plasma concentrations were significantly higher 24 h and 72 h after the marathon race . Hemoglobin and hematocrit levels decreased 72 h after the marathon race . We also observed an increased intercellular adhesion molecule-1 ( ICAM-1 ) expression and decreasedTNF receptor-1 ( TNFR1 ) expression immediately after and 24 h after the marathon race . We observed an increased DNA fragmentation and L-selectin and Fas receptor expressions in the recovery period , indicating a possible slow rolling phase and delayed neutrophil activation and apoptosis . Marathon racing affects neutrophils adhesion and survival in the course of inflammation , supporting the “ open-window ” post-exercise hypothesis The aim of this study was to investigate the effect of two different tapering period lengths on the concentration of plasma interleukin- 6 ( IL-6 ) , interleukin ( IL-1β ) and tumor necrosis factor-α ( TNF-α ) and performance in elite male cyclists . To this end , after completing 8 weeks progressive endurance exercise , twenty four high-level endurance cyclists were r and omly assigned to one of two groups : a control group of cyclists ( n = 12 ) continued performing progressive weekly training volume for 3 weeks while a taper group of cyclists ( n = 12 ) proceeded with a 50 % reduction in weekly training volume relative to the control group . A simulated 40 min time trial ( 40TT ) performance ride was used as the criterion index of performance before and after the tapering period to evaluate the physiological and performance effects of each protocol . Blood sample s were collected immediately post-40TT from all participants at the beginning of week 1 , and the end of weeks 4 , 8 , 9 and 11 . IL-1β , IL-6 and TNFα were assayed using a st and ard commercial ELISA kits ( Quantikine ; R & D Systems , Minneapolis , MN ) . The mean time to complete the 40TT in the taper group decreased significantly ( p < 0.01 ) after both 1 and 3 weeks with reduced training volume relative to the control group . There were significant reductions in ( p < 0.001 ) IL-1β , IL-6 and TNFα concentrations in the taper group relative to the control group at the end of the 3 week tapering period , but not at the end of the 1 week tapering period . These results demonstrate that both a 1 and a 3 week taper period will result in improved physical performance in trained cyclists but only a 3 week taper period will result in attenuation of post-exercise pro- inflammatory cytokines when compared to those continuing a more intense training regimen . Key pointsThe excessive endurance exercise-induced elevations in pro-inflammatory cytokines would , in turn , stimulate the release of anti-inflammatory cytokines . Elevations in pro-inflammatory cytokines indicate athletes are highly susceptible to infections.1 and 3-week taper periods will reduce circulating pro-inflammatory cytokine levels thereby possibly limiting the chances of infection and potentially reducing the effects of these cytokines in inducing fatigue-like symptoms in athletes Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Abstract To study the effects of exercise on circulating leukocytes and leukocyte subsets , physically active ( n = 32 ) and sedentary ( n = 32 ) male and female subjects were r and omly assigned to an exercise or control condition . Exercise involved a continuous incremental protocol consisting of cycling for three periods of 6 min at power outputs corresponding to 55 % , 70 % and 85 % maximal oxygen uptake ( $ $ \dot V{\text{O}}_{{\text{2max}}}$$ . Blood sample s were drawn from a venous catheter at baseline , and at 6 min , 12 min , and 18 min after beginning the exercise and 2 h following completion of exercise . Resting- and exercise-induced alterations in total leukocytes were independent of gender and subject fitness level . Relative to baseline , each increment in workload result ed in a rapid increase in the number of circulating leukocytes . Increases in neutrophils , lymphocytes and monocytes accounted for the exercise-induced leukocytosis . With regard to lymphocytes , exercise result ed in a significant increase in the number of T cells ( CD3 + ) , T helper cells ( CD4 + ) , T suppresser ( CD8 + ) and natural killer ( NK ) cells ( CD3−/CD16+/CD56 + ) . The largest percentage increase occurred in the NK cell population . The CD4 + : CD8 + ratio decreased ( P < 0.001 ) throughout exercise due to a larger increase in the number of CD8 + cells relative to CD4 + cells . An exercise-induced neutrophilia , lymphocytopenia , and eosinophelia was observed 2 h into recovery . Exercise result ed in significant increases in plasma epinephrine and norepinephrine levels . There was no indication of a hypothalamic-pituitarty-adrenal response during exercise . The results indicate that the rapid , albeit transient , alteration in the number of circulating leukocytes during and following an acute progressive incremental exercise test are independent of gender and fitness This study determined the influence of gender , menstrual phase ( MP ) , and oral contraceptive ( OC )  use on immunological changes in response to endurance exercise .  Twelve women and 11 men similar in age , aerobic power , and activity level cycled for 90 min at 65 % maximal aerobic power . Women were OC users ( n = 6 ) or nonusers ( NOC ) and cycled during the follicular ( Fol ) and the luteal ( Lut ) phases . Venous blood was collected before and after exercise to determine leukocyte counts , IL-6 concentrations , and cortisol . Higher resting levels of neutrophils ( approximately 1.5-fold ) and cortisol ( approximately 2.5-fold ) were found in OC vs. NOC and men . Exercise-induced immune cell count and IL-6 changes were similar between men and NOC , except for an approximately 38 % greater lymphocyte response in NOC vs. men ( P = 0.07 ) . Neutrophil , monocyte , and lymphocyte responses to exercise during Lut in OC were greater than during Fol and also greater than the responses in men ( P < or = 0.003 ) . Changes in immune cell counts were consistently greater during Lut in OC vs. NOC , regardless of MP , but only neutrophil responses reached statistical significance ( P = 0.01 ) . The exercise-induced change in IL-6 was approximately 80 % greater in NOC vs. OC during Fol ( P = 0.06 ) , but it was similar between these groups during Lut . Cortisol changes with exercise were not different between groups or MP . These results highlight the necessity to control for gender , and in particular OC use , when design ing studies evaluating exercise and immunology Cell-cell and cell-matrix contacts are dependent on cell surface density , localization , and avidity state of adhesion molecules . These adhesion molecules are involved in all steps of the leukocyte 's adhesion process . Selectins , molecules of the immunoglobulin superfamily , and integrins are necessary for an initial tethering , triggering , firm attachment , and transendothelial migration of leukocytes . Hormones , cytokines , other pro-inflammatory agents , and shedded receptors like the LPS-receptor significantly alter the adhesion process . Infectious and noninfectious inflammatory processes are capable of inducing an altered adhesion of leukocytes to endothelial cells . The result is a preferential homing of leukocytes to sites of inflammation . Acute bouts of exercise may induce a release or secretion of many of the aforementioned substances involved in the adhesion process . The acute immune response to exercise is strongly influenced by the activation of the sympathetic nervous system and the hypothalamo-pituitary-adrenal axis . During the first 10 - 30 min of exercise an almost maximal increase of T and B lymphocytes , monocytes , and NK cells from the marginal pool into the blood circulation is induced . This demargination of cells is likely an effect mediated by beta 2 adrenergic receptors and probably due to a change of the avidity state of adhesion molecules . Strenuous exercise is associated with an increase of serum cortisol result ing in a delayed neutrocytosis and lymphocytopenia . Both phenomena are due to altered circulation patterns . It will be discussed how far adhesion molecules might contribute to this effect . Furthermore an evaluation of contradicting experimental results about surface expression of selectins and integrins will be provided Apoptosis or programmed cell death is a process of fundamental importance for regulation of the immune response . Several reasons suggest that apoptosis is involved in exercise-induced alterations of the immune system such as postexercise lymphocytopenia . Healthy volunteers performed two treadmill exercise tests ; the first was performed at 80 % maximal oxygen uptake until exhaustion ( exhaustive exercise ) and the second 2 wk later at 60 % maximal oxygen uptake with the identical running time ( moderate exercise ) .  Blood sample s were taken before , immediately after , and 1 h after the test . Lymphocytes were analyzed for apoptotic and necrotic cells by using FITC-labeled annexin V-antibodies and nuclear propidium iodide uptake , respectively . In addition , apoptotic/necrotic cells were measured after a 24-h incubation of lymphocytes in the presence of camptothecin or phytohemagglutinin . Finally , plasma membrane expression of CD95-receptor and CD95-receptor lig and was investigated . Immediately after the exhaustive exercise , the percentage of apoptotic cells increased significantly , whereas it remained unchanged after the moderate exercise . Similar results were obtained after 24-h incubation of lymphocytes in medium alone or in the presence of camptothecin , but not with phytohemagglutinin . We found an upregulation of CD95-receptor expression after both exercise tests . However , only after exhaustive exercise a characteristic shift in CD95 expression profile toward cells with a high receptor density was observed . Expression of the CD95-receptor lig and remained unchanged after both exhaustive and moderate exercise . These results suggest that apoptosis may contribute to the regulation of the immune response after exhaustive exercise . Whether this mechanism can be regarded either as beneficial , i.e. , deletion of autoreactive cells , or harmful , i.e. , suppression of the immune response , awaits further investigations This study was conducted to determine the effects of an aerobic exercise training program on  sub population s of lymphocyte phenotypes . Fourteen healthy but sedentary males , 18 - 40 years of age , were r and omly assigned to either an aerobic exercise training or control condition . Aerobic exercise training consisted of three 45-minute sessions of cycle ergometry exercise per week at 70 - 80 % of age-predicted maximum heart rate for ten weeks . The aerobic exercise training result ed in a significant decrease in submaximal heart rate from 176 to 150 beats per minute to a fixed work rate of 150 watts ( p < .01 ) . This training effect was accompanied by increases in the resting level of the following lymphocyte sub population s : CD2 ( 1717 vs 2183 mm3 ; p < .01 ) , CD4 ( 942 vs 1280 mm3 ; p < .01 ) , CD45RA+CD4 + ( 312 vs 595 mm3 ; p < .01 ) , CD8 ( 655 vs 816 mm3 ; p < .05 ) , and CD20 ( 162 vs 244 mm3 ; p < .01 ) cell counts . These findings indicate that several lymphocyte sub population s are increased following a 10-week program of aerobic exercise training Abstract To study the effects of exercise on natural killer ( NK ) cell number and activity ( NKCA )  healthy male ( n = 32 ) and female ( n = 32 ) subjects were r and omly assigned to an exercise or control condition . Exercise involved a continuous incremental protocol consisting of cycling for three periods of 6 min at work rates corresponding to 55 % , 70 % and 85 % peak oxygen uptake ( $ $ \dot V{\text{O}}_{2{\text{peak}}}$$ ) . Blood sample s were drawn at baseline , at 6 min , 12 min and 18 min during exercise , and at 2 h following completion of exercise . Relative to both baseline and control conditions , exercise result ed in an increase in the number of circulating lymphocytes . The proportion of T cells ( CD3 + ) and B cells ( CD19 + ) significantly decreased , and NK cells ( CD3−CD16+ 
    Output:
    
Conclusion : Thus , it can be concluded that the evidence indicates that acute and chronic interventions may modify most immune markers , but aspects such as gender , contraceptive pill use in women , physical capacity of the investigated individuals , environment , and type and intensity of the exercises may interfere with these markers as well as the data analysis .