Transcript Short-term increase in plasma IL-6 after downhill running

Short-term increase in plasma IL-6 after downhill
running is associated with increased core
temperature during subsequent exercise-heat stress
1
Fortes ,
1,2
Felice ,
1
Dolci ,
Matthew
Umberto Di
Alberto
1
1
1
Naushad Junglee , Jamie Macdonald and Neil Walsh
1Extremes
Research Group, Bangor University, Gwynedd, Wales.
2Department of Biomedical Sciences and Technologies, University of L'Aquila, Italy.
SUMMARY
##
EIMD
CON
8
**
6
Treatment
4
EIM D
or
CON
2
#
**
**
EIMD
40.0
T r e during HS (  C)
Plasma IL-6
concentration (pg/ml)
• We investigated the effect of prior muscle damaging exercise, and associated
inflammation upon subsequent thermoregulation during exercise in the heat.
• Exercise-induced muscle damage (EIMD) increased heat storage during a
subsequent heat stress test (40 min running in 33ºC, 50%RH) compared with
control treatment, such that final rectal temperature was 0.5ºC higher.
• The greater inflammatory response following EIMD, as measured by circulating
interleukin (IL)-6 was positively associated with heat storage (r = 0.58), and final
core temperature (r = 0.67) during subsequent exercise heat stress.
40.5
10
CON
39.5
39.0
#
38.5
37.5
**
Pre HS
Post HS
0
4
8
INTRODUCTION
Fig 2. Plasma IL-6 response at baseline, and pre
and post exercise heat stress (HS). HS was
conducted 30 min after either exercise-induced
muscle damage (EIMD) or control exercise
(CON). **P < 0.01 vs. baseline; # P < 0.05, and
## P < 0.01 between trial differences. n = 13.
 T r e during HS (  C)
2.5
##
2.0
1.5
1.0
0.5
EIMD
CON
Fig 4. Heat storage (Δ Tre) during HS performed
30 min after either exercise-induced muscle
damage (EIMD) or control exercise (CON). ## P
< 0.01 between trial difference. n = 13.
Plasma creatine kinase activity (253 ± 76 vs. 133 ± 70 U/L) and DOMS (52 ± 15 vs. 17
± 9mm) were both greater on EIMD than CON 24-h following treatment (P<0.001).
Plasma IL-6 concentration was not different between trials at baseline, but was greater
on EIMD than CON immediately pre (P<0.05), and post HS (P<0.01, Fig 2). Tre was
significantly greater during HS on EIMD from 16 min onwards during HS (Fig 3)
resulting in a 0.5C higher final Tre (P<0.01). Heat storage throughout HS was also
greater following EIMD (P<0.01, Fig 4). There was no difference in mean Tsk during
HS between trials (P=0.38). The rapid increase in local forearm sweat rate occurred
at a higher Tre following EIMD, with no difference in sweat sensitivity from 6-40 min
during HS between trials (Fig 5). The acute inflammatory response after treatment,
measured as the difference in plasma IL-6 response between EIMD and CON,
correlated well with the difference between trials in the ΔTre during HS (r=0.58,
P<0.05), and with the final Tre during HS (r=0.67, P< 0.05, Figs 6A & B). Mean VO2
during HS was greater on EIMD than CON (3.0 ± 0.3 vs. 2.8 ± 0.3 L/min, P<0.01).
Despite this decreased economy, the difference in VO2 between trials did not correlate
well with the difference between trials in the ΔTre during HS (r=0.24, P=0.43) nor the
final Tre (r=0.40, P=0.17).
0.4
EIMD
0.2
CON
37.5
38.0
38.5
39.0
39.5
40.0
Fig 5. Mean local forearm sweat rate as a
function of Tre during HS performed 30 min after
either exercise-induced muscle damage (EIMD)
or control exercise (CON). n = 11.
1.5
Final T r e after HS
(EIMD - CON)  C
 T r e during HS
(EIMD - CON)  C
RESULTS
0.6
A
1.0
0.5
r = 0.58
r2 = 0.34
P = 0.038
0.0
-0.5
Rectal core temperature (Tre), skin temperature (4 sites, Tsk), oxygen uptake (Douglas
bag method, VO2), and local forearm sweat rate (ventilated capsule) were measured
throughout HS. Blood samples were collected prior to treatment (baseline), and
immediately pre and post HS, and assessed for plasma IL-6 concentration by ELISA
(R&D systems, USA). Muscle damage was assessed 24-h post treatment by plasma
creatine kinase activity and delayed onset of soreness (DOMS) by 100mm visual
analogue scale. Data were analysed using ANOVA, paired t-tests and Pearson’s
correlations. The study was approved by the departmental ethics committee.
0.8
Tre during HS (C)
1.5
Fig 1. Schematic of experimental procedures (EIMD, exercise-induced muscle damage).
1.0
0.0
37.0
0.0
12 16 20 24 28 32 36 40
Time during HS (min)
Fig 3. Rectal core temperature (Tre) responses to
exercise heat stress (HS) performed 30 min after
either exercise-induced muscle damage (EIMD)
or control exercise (CON). **P < 0.01 vs. time 0; #
P < 0.05, and ## P < 0.01 between trial
differences. n = 13.
Mean local forearm
sweat rate (mg/cm2/min)
With informed consent, thirteen non-heat-acclimated healthy males (mean age ± SD,
20 ± 2 years) completed two, randomised and counterbalanced treadmill running trials
separated by two-weeks. Participants performed a treatment which involved running
for 60 min at 64% VO2max at room temperature; on one occasion on a -10% gradient
(EIMD), and another on a +1% gradient (CON). The running speed to elicit 64%
VO2max on both trials was verified during preliminary testing. Following both
treatments, participants rested for 30 min, timed to coincide with elevated circulating
inflammatory mediators, and then performed 40 min exercise heat-stress (HS) at the
predetermined running speed to reflect 65% VO2max (9.8 ± 1.2 km/h) (Fig 1).
##
36.5
Baseline
EXPERIMENTAL PROCEDURES
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38.0
37.0
0
Athletes and military personnel undergoing heavy training are often expected to
perform repeated bouts of arduous physical activity in the same day, often in hot
environments. It has been shown that prior muscle injury may alter thermoregulation
during subsequent exercise heat-stress (Montain et al. 2000). However, it remains
unclear whether the acute inflammatory response that follows muscle damaging
exercise (e.g. increase in circulating pyrogen IL-6) increases heat storage during
subsequent exercise-heat stress. Using anti-IL-6 antibodies in rodents, a role for
circulating IL-6 in the febrile response via the cyclo-oxygenase (COX) - 2 pathway has
been identified (Rummel et al., 2006). The use of COX inhibitors in humans suggests
that prostaglandin-mediated inflammatory processes may also contribute to rises in
core temperature during exercise (Bradford et al., 2007). As such, we tested the
hypothesis that acute inflammation following EIMD, using a downhill running model,
increases core temperature during subsequent endurance exercise in the heat.
#
##
##
B
1.0
0.5
r = 0.67
r 2 = 0.45
P = 0.013
0.0
-0.5
-1
0
1
2
3
4
-1
 Plasma IL-6 Baseline - pre HS
(EIMD - CON) pg/ml
0
1
2
3
4
 Plasma IL-6 Baseline - pre HS
(EIMD - CON) pg/ml
Fig 6. Scatterplots between the difference in plasma interleukin (IL)-6 concentration between EIMD and
CON, with the change in Tre response between trials during exercise heat stress (A), and with the
difference between trials in the final Tre attained after exercise heat stress (B). n = 13.
CONCLUSIONS
These data show that a bout of exercise-induced muscle damage, evoked by downhill
running, increases the short-term plasma IL-6 response to exercise; and that this is
associated with increased core temperature during subsequent exercise in the heat.
Increased plasma IL-6 following exercise-induced muscle damage accounted for a larger
proportion of variance in heat storage and final rectal core temperature during subsequent
exercise heat stress, than altered economy.
These results have practical relevance for athletes and soldiers undertaking multiple bouts
of heavy exercise with an eccentric component in the heat.
REFERENCES
Bradford , C.D. et al. (2007). Exercise can be pyrogenic in humans. Am. J. Physiol. Regul. Integr. Comp. Physiol. 292: R143-R149.
Montain, S.J. et al. (2000). Impact of muscle injury and accompanying inflammatory response on thermoregulation during exercise in the
heat. J. Appl. Physiol. 89: 1123-1130.
Rummel et al. (2006). Circulating interleukin-6 induces fever through a STAT3-linked activation of COX-2 in the brain. Am. J. Physiol. Regul.
Integr. Comp. Physiol. 291: R1316-R1326.
ACKNOWLEDGEMENTS
We would like to thank the following people for their valuable assistance during data collection: Michael Crockford, Liam West, Ryan HillierSmith, Lindsey Jankowski, Megan Butterworth, Ben Terzza, Daniel Kashi, Tom Riddle and Dominique Mauger. We are also indebted to the
participants for their time and co-operation.
http://extremes.bangor.ac.uk