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1 Immunology Center and Department of Pathology, Loma Linda University Medical Center, Loma Linda, California 92350; 2 Department of Health, Leisure, and Exercise Science and Department of Biology, Appalachian State University, Boone, North Carolina 28608; and 3 Department of Exercise Science, School of Public Health, University of South Carolina, Columbia, South Carolina 29208
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
ACKNOWLEDGEMENTS
FOOTNOTES
REFERENCES
ABSTRACT 
Nehlsen-Cannarella, S. L., O. R. Fagoaga, D. C. Nieman, D. A. Henson, D. E. Butterworth, R. L. Schmitt, E. M. Bailey, B. J. Warren, A. Utter, and J. M. Davis. Carbohydrate and the cytokine
response to 2.5 h of running. J. Appl.
Physiol. 82(5): 1662-1667, 1997.
This randomized,
double-blind, placebo-controlled study was designed to determine the
influence of 6% carbohydrate (C) vs. placebo (P) beverage ingestion on
cytokine responses (5 total samples over 9 h) to 2.5 h of
high-intensity running (76.7 ± 0.4% maximal
O2 uptake) by 30 experienced
marathon runners. For interleukin-6 (IL-6), a difference in the pattern
of change between groups was found, highlighted by a greater increase
in P vs. C immediately postrun (753 vs. 421%) and 1.5 h postrun (193 vs. 86%) [F(4,112) = 3.77, P = 0.006]. For
interleukin-1-receptor antagonist (IL-1ra), a difference in the pattern
of change between groups was found, highlighted by a greater increase
in P vs. C 1.5 h postrun (231 vs. 72%)
[F(2,50) = 6.38, P = 0.003]. No significant interaction effects were seen for bioactive IL-6 or IL-1
. The immediate postrun plasma glucose concentrations correlated negatively with those of plasma cortisol (r = 
0.67, P < 0.001); postrun plasma cortisol (r = 0.70, P < 0.001) and IL-6 levels
(r = 0.54, P = 0.003) correlated positively with
levels of IL-1ra. Taken together, the data indicate that carbohydrate
ingestion attenuates cytokine levels in the inflammatory cascade in
response to heavy exertion.
immune system; cortisol; interleukin-6; interleukin-l; interleukin-1-receptor antagonist
INTRODUCTION STRENUOUS PHYSICAL EXERCISE such as long-distance
running typically results in muscle soreness and injury. The response
to tissue injury after exercise is analogous to the acute-phase
response to inflammation resulting from infection (2). Intense exercise elicits some of the cytokines involved in inflammation, such as tumor
necrosis factor- Although heavy exertion is felt to affect both inflammatory and
anti-inflammatory components, few studies have provided cytokine data
from both sides of this control system (2, 6, 22). Drenth et al. (13)
collected plasma samples on 19 athletes before and after they ran 6 h
and reported a 286% increase in IL-6 and a 371% increase in IL-1ra
but no change in plasma concentrations of IL-1 or TNF- To our knowledge, no attempts have been made to alter plasma cytokine
levels during intensive and prolonged endurance exercise by nutritional
or chemical means (2, 22). Nutrient supplements have been studied for
their effect in modulating cytokine levels in efforts to improve the
immune dysfunction of surgery and cancer (24). Proinflammatory
cytokines activate the hypothalamic-pituitary-adrenocortical (HPA)
axis, providing a natural negative-feedback system through the
anti-inflammatory actions of epinephrine and cortisol that inhibit the
release of IL-1 and IL-6 from monocytes and macrophages (1, 2).
Carbohydrate supplementation during prolonged endurance exercise has
been associated with higher blood glucose and lower cortisol,
epinephrine, and growth hormone responses (10, 18, 20, 21, 25). Given
the role of stress hormones in regulating the inflammatory process and
the release of cytokines, we designed a randomized, double-blind,
placebo-controlled study to investigate the influence of carbohydrate
ingestion on the inflammatory cytokine response to 2.5 h of intensive
running. We studied IL-1 METHODS Subjects
(TNF-), interleukin (IL)-1/ (IL-1/), and IL-6, which work synergistically (2, 16). The inflammatory process
is limited or reversed through several pathways including the
production of anti-inflammatory cytokines [IL-1-receptor
antagonist (IL-1ra), IL-4, IL-10, cortisol, and prostaglandin
E2] (2).
. Despite the
difficulties inherent in measuring plasma cytokine concentrations (2,
8), other studies of subjects exercising intensively for 60 min or more
have reported increases in plasma concentrations of IL-6 (22, 27, 28) but a variable IL-1 response, with some reporting an increase (6, 29)
and others no change (27, 28). IL-1 has been found in both muscle and
urine after exercise (7, 27), so it is believed that this cytokine is
increased in response to exercise despite the difficulty in detecting
it in postexercise plasma (2). Reported inconsistencies in plasma
levels may be due to differing collection times and assay
sensitivities, but they are most likely due to its short half-life
(12). Moderate endurance exercise [e.g., 1 h of cycling at 60%
maximal O2 uptake (
O2 max)] appears
to have little effect on acute-phase response cytokines (26).
, IL-6, and IL-1ra to investigate effects on
the early and late phases of inflammation and on the anti-inflammatory
resolution phase, respectively. We hypothesized that carbohydrate vs.
placebo supplementation would keep plasma glucose levels at a higher
level, attenuating the rise in epinephrine and cortisol and both pro-
and anti-inflammatory cytokines.
30 km/wk during the previous year; completion of at least
two marathon race events; and 4 or more yr of running experience.
Experimental Design
Runners were unevenly randomized into carbohydrate (n = 17)- or placebo (n = 13)-supplement groups. Runners from each group recorded food intake for 3 days before the simulated marathon run, choosing foods from a list that ensured a carbohydrate intake of ~60% of total calories. Nutrient intake was assessed by using the computerized dietary-analysis system Food Processor Plus, version 6.0 (ESHA Research, Salem, OR).This study was conducted during the months of May and June. During the
subjects' first appointment, their height, weight, body composition,
and maximal cardiorespiratory fitness were measured. Body composition
was assessed from hydrostatic weighing, and
O2 max was determined
by utilizing a graded maximal treadmill protocol (5, 23).
O2 uptake and ventilation were
measured by using the MedGraphics CPX metabolic system (MedGraphics St.
Paul, MN). Maximal heart rate was measured by using the Quinton Q4000
Stress Test System (Quinton Instrument, Seattle, WA). Training history and demographic factors were assessed through use of a questionnaire.
Within 2 wk of their first appointment, subjects reported to the Human Performance Laboratory in a 12-h fasted and rested condition at 0700. Subjects indicated that they had avoided intensive exercise the day before testing and all exercise for at least 12-15 h and that they were free of symptoms associated with respiratory infections. After the subjects rested for 10-15 min, a blood sample was taken from each. Next, the runners consumed 0.75 liter of a 6% carbohydrate (Gatorade, Quaker Oats, Barrington, IL) or placebo beverage before the run. The beverages were prepared by the Gatorade Sports Science Institute. Treatments were double blind, and carbohydrate and placebo beverages were identical in appearance and taste. Except for carbohydrate concentration, the two fluids were identical in sodium (~19.0 meq/l) and potassium (~3.0 eq/l) concentration and in pH (~3.0).
The marathoners ran on treadmills from 0730 to 1000 at a pace adjusted to elicit a workload ~75-80% of VO2max. Metabolic and heart rate measurements were made every 20 min during the run to ensure that subjects were maintaining the appropriate workload. Runners ingested 0.250 liter of carbohydrate or placebo fluid every 15 min during the run. Immediately after the 2.5-h run, at 1000, blood samples were obtained from the runners, followed by samples taken at 1130, 1300, and 1600. Subjects drank 500 ml/h of carbohydrate or placebo fluid during the first 1.5 h of recovery and then 250 ml/h during the last 4.5 h of recovery. After the 1130 blood sampling, subjects ate a meal ad libitum, choosing foods from the same food list they had adhered to during the 3 days before the study.
Cytokine Measurements
Five blood samples per subject were drawn from an antecubital vein into heparinized tubes with subjects in the seated position (after 10-15 min of rest, except for the immediate postrun sample). The collection tubes were immediately chilled and centrifuged, with plasma samples frozen at80°C until analysis (cytokine, hormone,
and glucose levels). IL-6 (both total plasma levels and bioactive) and
cortisol were measured from all five blood samples. Several parameters
(IL-1, IL-1ra, glucose, and catecholamines) that were anticipated to
be near baseline levels by 1.5 h postexercise were not measured at the
3- and 6-h postrun time points.
Total plasma IL-1 and IL-6 measurements.
IL-1 and IL-6 were measured with MEDGENIX solid-phase
enzyme-amplified sensitivity immunoassay (INCSTAR, Stillwater, MN) enzyme-linked immunoabsorbent assay kits. These assays are based on an
oligoclonal system, in which a blend of monoclonal antibodies directed
against distinct epitopes of each interleukin molecule is used to
capture antibodies. The minimum detectable concentration of plasma
IL-1 and IL-6 is 2 pg/ml.
Plasma bioactive IL-6 assay.
A standard proliferative bioassay (9) was used to measure the activity
of human IL-6. Briefly, multiple dilutions of plasma samples (plasma
inhibitors of IL-6 were inactivated by heating) and a standard (human
recombinant IL-6; Collaborative Biomedical Products/Becton-Dickinson
Labware, Bedford, MA) were tested in culture for their ability to
stimulate proliferation of IL-6-responsive 7TD1 mouse hybridoma cells
(American Type Culture Collection, Rockville, MD). The assays were done
in triplicate. The amount of proliferation was assessed by the level of
[3H]thymidine uptake.
Interassay variability was monitored by using an internal control in
each assay. The final IL-6 mean concentration for the internal controls
was 4.51 ± 0.65 U/ml, giving us confidence in the sensitivity and
reproducibility of this assay. The IL-6 bioassay has a detection limit
of ~1 pg/ml of active cytokine.
Total plasma IL-1ra.
Total plasma IL-1ra was measured with the use of a quantitative
sandwich enzyme-linked immunoabsorbent assay technique by using
monoclonal antibodies specific for IL-1ra as capture antibodies (R&D
Systems, Minneapolis, MN). The minimum detectable level of plasma
IL-1ra is <14 pg/ml.
Hormones, Glucose, and Plasma Volume
Plasma cortisol was assayed by using a competitive solid-phase 125I radioimmunoassay technique (Diagnostic Products, Los Angeles, CA). For plasma epinephrine and norepinephrine, blood samples were drawn into chilled tubes containing EGTA and glutathione (no. RPN532 Vacutainer tubes, Amersham) and centrifuged, and the plasma was stored at80°C until
analysis. Plasma concentrations of epinephrine were determined by
high-pressure liquid chromatography with electrochemical detection
(19). Plasma was analyzed spectrophotometrically for glucose (prerun,
immediately postrun, and 1.5-h postrun samples) (17).
Plasma volume changes were estimated by using the method of Dill and
Costill (11).
Statistical Analysis
Data are expressed as means ± SE. Leukocyte subsets, hormone values, and all immune function measurements were analyzed by using 2 (carbohydrate and placebo groups) × 3 or 5 (times of measurement) repeated-measures analysis of variance. The change from baseline for the immediate postexercise and 1.5-, 3-, and 6-h recovery values was compared between groups by using Student's t-test. For these four multiple comparisons, a Bonferroni adjustment was made, with statistical significance set at P < 0.013, and values between this and 0.05 were treated as trends. Pearson product-moment correlations for glucose, cortisol, epinephrine, and various cytokine measurements were calculated within the group of marathon runners to test the strength of these associations.RESULTS
Table 1 summarizes subject characteristics for the runners in the carbohydrate and placebo groups. Groups did not differ significantly in any of the training and fitness parameters measured. The 30 runners can be characterized as nonelite but highly experienced and committed to marathon running.
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Nutrient analysis of the 3-day food records revealed no significant differences between groups. Energy intake for all subjects combined was 2,368 ± 114 calories/day, with the proportion of carbohydrate at 62.6 ± 1.5%, fat at 22.3 ± 1.2%, and protein at 15.7 ± 0.4%.
The carbohydrate and placebo groups did not differ significantly in any
of the performance measurements taken during the 2.5-h run, except for
the average respiratory exchange ratio (0.93 ± 0.01 and 0.89 ± 0.01, respectively, P = 0.009) and the
ending rating of perceived exertion by using the 6-20 scale (14.8 ± 0.3 and 16.3 ± 0.4, respectively,
P = 0.004). As a group, the 30 marathon runners averaged 11.9 ± 0.2 km/h during the 2.5-h run at a
heart rate of 151 ± 2 beats/min or 85.5 ± 0.5% of the maximum
heart rate, an O2 uptake of 40.9 ± 0.8 ml · kg
1 · minl
or 76.7 ± 0.4% of
O2 max, a
ventilation volume of 89.3 ± 3.2 l/min or 63.2 ± 1.4% of
maximal ventilation, and a breath rate of 43.4 ± 1.6 breaths/min.
The laboratory temperature averaged 23.8 ± 0.2°C,
with a relative humidity of 51.9 ± 0.6%. All runners consumed
fluids according to the research design, including 2.5 liters during
the 2.5-h run. The average runner lost 0.35 ± 0.14 kg of body
weight (0.4 ± 0.2%). Plasma volume changes were minimal, and the pattern of change over all time points did not differ significantly between the two groups
[F(3.26) = 0.90;
P = 0.453]; for the pre- to
immediate postexercise period, plasma volume change for the
carbohydrate and placebo groups was only 1.5 ± 0.4 and 1.0 ± 0.4%, respectively.
The cytokine data are summarized in Table 2
and Figs. 1 and 2. The
pattern of change over time between groups was not significantly different for bioactive IL-6 or total plasma IL-1 but was
significant for total plasma IL-6
[F(4,112) = 3.77, P = 0.006] and IL-1ra [F(2,50) = 6.3, P = 0.003]. For total plasma
IL-6, a greater increase from prerun levels was measured for the
placebo vs. carbohydrate groups at the immediate postrun (753 and
421%, respectively, P = 0.028) and
1.5-h postrun (193 vs. 86%, respectively,
P = 0.018) time points. By 1.5 h
postrun, plasma IL-lra had risen 231 vs. 72% in the placebo and
carbohydrate groups, respectively (P = 0.013). Significant time effects were found for IL-6 (bioactive) but
not IL-l (total). For all subjects combined, IL-6 (bioactive) rose
49% immediately after the run, returning close to prerun levels by 1.5 h postrun.
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Figure 3 and Table 3
summarize the plasma cortisol, catecholamine, and glucose data. The
patterns of change over time between groups for cortisol
[F(4,25) = 3.46, P = 0.022] and glucose
[F(2,27) = 10.0, P = 0.001], but not epinephrine
[F(2,26) = 1.94, P = 0.164], were significantly
different, with cortisol higher and glucose concentrations lower in the
placebo group after the 2.5-h run. The immediate postrun glucose
concentration correlated negatively with cortisol
(r = 0.67,
P < 0.001) and epinephrine
(r = 0.54, P = 0.002). The 1.5-h postrun total
IL-1ra correlated positively with the averages of immediate postrun and
1.5-h postrun cortisol levels (r = 0.70, P < 0.001)
(Fig. 4) and total plasma IL-6
(r = 0.54, P = 0.003). No significant correlation
between postrun cortisol and total plasma IL-6 was found.
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, Carb group; star, placebo group.
DISCUSSION
In agreement with Drenth et al. (13), we showed that intensive,
prolonged exercise is associated with a strong increase in plasma
concentrations of both IL-6 and IL-1ra but not IL-1. We have
extended this information, showing that carbohydrate vs. placebo
ingestion was associated with higher plasma glucose and lower plasma
cortisol, IL-6, and IL-1ra concentrations. These data suggest that
carbohydrate ingestion attenuates both the pro- and anti-inflammatory
responses to heavy exertion, a conclusion strengthened by the
significant correlations between plasma glucose and cortisol, cortisol
and IL-1ra, and IL-1ra and IL-6.
As a part of the body's natural negative-feedback system, proinflammatory cytokines activate the HPA axis and the sympathoadrenergic system, exerting strong anti-inflammatory actions (2). Epinephrine and cortisol both inhibit the release of IL-1 and IL-6 from isolated monocytes (1). We sought to alter the stress hormonal response to heavy exertion through carbohydrate ingestion and then study whether the plasma inflammatory cytokine response was affected. Release of adrenocorticotropic hormone and cortisol during exercise has been linked, in part, to decreases in blood glucose concentrations (10, 18, 20, 21), with a variable effect on epinephrine (20, 21). Although decreases in blood glucose are not typical during and after intensive long-distance running, the data from the present study do suggest that carbohydrate ingestion is associated with higher plasma glucose and lower plasma cortisol levels after 2.5 h of intensive running. For all subjects, there was a strong negative correlation between postrun plasma glucose and cortisol levels, with a moderate negative effect on epinephrine.
The onset of inflammation is brought about by tissue macrophages, smooth muscle cells, and fibroblasts responding to muscle cell injury and producing cytokines of the IL-1 and TNF families; these are called early or "alarm" cytokines (3, 14). IL-1 and TNF act on fibroblasts and endothelial cells to produce a secondary front of cytokines, which includes IL-6 and IL-8 (3). The main mediator of the acute-phase response is IL-6, which, in turn, is regulated by IL-1 (15). The elevation of IL-6 helps induce synthesis of acute-phase proteins (inflammatory); it also upregulates IL-1ra production and activates the HPA axis, both anti-inflammatory. These parameters correlated in our study. As reviewed by Bagby et al. (2), few studies have examined the tissue site of cytokine production in response to exercise. Ullum et al. (28) were unable to detect exercise-induced changes in blood mononuclear cell mRNA for various cytokines and surmised that a tissue other than blood produces IL-6 and IL-1. Probable sources are the active muscle, other metabolically active tissues in which proinflammatory events are occurring (2, 4, 7), and the brain (30).
The data from the present study suggest that carbohydrate must be having some effect starting in the metabolically active tissue areas because of its effect in lowering IL-6, an important inducer of the inflammatory cascade. In the carbohydrate group, total plasma IL-6 was lower than in the placebo group, which was then linked to lower total IL-1ra and cortisol. Although plasma glucose was higher in the carbohydrate group, and correlated strongly and negatively to cortisol, it is likely that the first step in the chain of events occurred within the metabolically active tissues. Alternatively, the energy demands of the brain may not have been satisfied throughout the 2.5-h run in the placebo group, and this deficiency could have generated a stress signal. Both of these pathways may have simultaneously contributed to the stress response.
Carbohydrate ingestion had a significant effect on the pattern of response of total plasma IL-6 but not bioactive IL-6 after 2.5 h of running. For all subjects combined, total plasma IL-6 rose 551% immediately after exercise compared with 49% for bioactive IL-6. We used a standard proliferative bioassay, in which plasma samples were tested in culture for their ability to stimulate proliferation of IL-6-responsive 7TD1 mouse hybridoma cells (9). We expected to find that the proliferative response was higher in the placebo vs. the carbohydrate group because of its higher total plasma IL-6. These are the first bioactive IL-6 data to be presented in the exercise immunology literature, and further research is warranted to establish the usefulness of this assay under exercise conditions.
ACKNOWLEDGEMENTS
We acknowledge the assistance of the following individuals in this research project: Leslie Brooks, Melinda Ekkens, Eric Garges, Alex Koch, Jepera Parker, Marvin Rainwater, Angie Ward, and Franklin Williams.
FOOTNOTES
Address for reprint requests: D. C. Nieman, Dept. of Health, Leisure, and Exercise Science, Appalachian State Univ., Boone, NC 28608.
Received 11 November 1996; accepted in final form 21 January 1997.
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K. J. Green, S. J. Croaker, and D. G. Rowbottom Carbohydrate supplementation and exercise-induced changes in T-lymphocyte function J Appl Physiol, September 1, 2003; 95(3): 1216 - 1223. [Abstract] [Full Text] [PDF]
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N. Hiscock, E. W. Petersen, K. Krzywkowski, J. Boza, J. Halkjaer-Kristensen, and B. K. Pedersen Glutamine supplementation further enhances exercise-induced plasma IL-6 J Appl Physiol, July 1, 2003; 95(1): 145 - 148. [Abstract] [Full Text] [PDF]
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D. C. Nieman, J. M. Davis, D. A. Henson, J. Walberg-Rankin, M. Shute, C. L. Dumke, A. C. Utter, D. M. Vinci, J. A. Carson, A. Brown, et al. Carbohydrate ingestion influences skeletal muscle cytokine mRNA and plasma cytokine levels after a 3-h run J Appl Physiol, May 1, 2003; 94(5): 1917 - 1925. [Abstract] [Full Text] [PDF]
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T. Vassilakopoulos, M.-H. Karatza, P. Katsaounou, A. Kollintza, S. Zakynthinos, and C. Roussos Antioxidants attenuate the plasma cytokine response to exercise in humans J Appl Physiol, March 1, 2003; 94(3): 1025 - 1032. [Abstract] [Full Text] [PDF]
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O. Ronsen, T. Lea, R. Bahr, and B. K. Pedersen Enhanced plasma IL-6 and IL-1ra responses to repeated vs. single bouts of prolonged cycling in elite athletes J Appl Physiol, June 1, 2002; 92(6): 2547 - 2553. [Abstract] [Full Text] [PDF]
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M. Yamada, K. Suzuki, S. Kudo, M. Totsuka, S. Nakaji, and K. Sugawara Raised plasma G-CSF and IL-6 after exercise may play a role in neutrophil mobilization into the circulation J Appl Physiol, May 1, 2002; 92(5): 1789 - 1794. [Abstract] [Full Text] [PDF]
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 A. Steensberg, A. D. Toft, P. Schjerling, J. Halkjar-Kristensen, and B. K. Pedersen Plasma interleukin-6 during strenuous exercise: role of epinephrine Am J Physiol Cell Physiol, September 1, 2001; 281(3): C1001 - C1004. [Abstract] [Full Text] [PDF]
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K. Krzywkowski, E. W. Petersen, K. Ostrowski, H. Link-Amster, J. Boza, J. Halkjaer-Kristensen, and B. K. Pedersen Effect of glutamine and protein supplementation on exercise-induced decreases in salivary IgA J Appl Physiol, August 1, 2001; 91(2): 832 - 838. [Abstract] [Full Text] [PDF]
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D. C. Nieman, D. A. Henson, L. L. Smith, A. C. Utter, D. M. Vinci, J. M. Davis, D. E. Kaminsky, and M. Shute Cytokine changes after a marathon race J Appl Physiol, July 1, 2001; 91(1): 109 - 114. [Abstract] [Full Text] [PDF]
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 S. G. Rhind, J. W. Castellani, I. K. M. Brenner, R. J. Shephard, J. Zamecnik, S. J. Montain, A. J. Young, and P. N. Shek Intracellular monocyte and serum cytokine expression is modulated by exhausting exercise and cold exposure Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2001; 281(1): R66 - R75. [Abstract] [Full Text] [PDF]
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R. L. Starkie, J. Rolland, D. J. Angus, M. J. Anderson, and M. A. Febbraio Circulating monocytes are not the source of elevations in plasma IL-6 and TNF-{alpha} levels after prolonged running Am J Physiol Cell Physiol, April 1, 2001; 280(4): C769 - C774. [Abstract] [Full Text] [PDF]
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B. K. Pedersen and A. D. Toft Effects of exercise on lymphocytes and cytokines Br. J. Sports Med., August 1, 2000; 34(4): 246 - 251. [Abstract] [Full Text] [PDF]
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 B. K. Pedersen and L. Hoffman-Goetz Exercise and the Immune System: Regulation, Integration, and Adaptation Physiol Rev, July 1, 2000; 80(3): 1055 - 1081. [Abstract] [Full Text] [PDF]
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 A. GORNIKIEWICZ, T. SAUTNER, C. BROSTJAN, B. SCHMIERER, R. FÜGGER, E. ROTH, F. MÜHLBACHER, and M. BERGMANN Catecholamines up-regulate lipopolysaccharide-induced IL-6 production in human microvascular endothelial cells FASEB J, June 1, 2000; 14(9): 1093 - 1100. [Abstract] [Full Text]
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I. K. M. Brenner, J. W. Castellani, C. Gabaree, A. J. Young, J. Zamecnik, R. J. Shephard, and P. N. Shek Immune changes in humans during cold exposure: effects of prior heating and exercise J Appl Physiol, August 1, 1999; 87(2): 699 - 710. [Abstract] [Full Text] [PDF]
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D. C. Nieman, S. L. Nehlsen-Cannarella, O. R. Fagoaga, D. A. Henson, A. Utter, J. M. Davis, F. Williams, and D. E. Butterworth Effects of mode and carbohydrate on the granulocyte and monocyte response to intensive, prolonged exercise J Appl Physiol, April 1, 1998; 84(4): 1252 - 1259. [Abstract] [Full Text] [PDF]
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D. C. Nieman, D. A. Henson, S. R. McAnulty, L. McAnulty, N. S. Swick, A. C. Utter, D. M. Vinci, S. J. Opiela, and J. D. Morrow Influence of vitamin C supplementation on oxidative and immune changes after an ultramarathon J Appl Physiol, May 1, 2002; 92(5): 1970 - 1977. [Abstract] [Full Text] [PDF]
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