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Eur J Appl Physiol
DOI 10.1007/s00421-009-1139-x
123
ORIGINAL ARTICLE
Cytokine and hormone responses to resistance training
Mikel Izquierdo · Javier Ibañez · Jose A. L. Calbet · Ion Navarro-Amezqueta ·
Miriam González-Izal · Fernando Idoate · Keijo Häkkinen · William J. Kraemer ·
Mercedes Palacios-Sarrasqueta · Mar Almar · Esteban M. Gorostiaga
Accepted: 16 July 2009
© Springer-Verlag 2009
Abstract This study examined the eVects of heavy
resistance training on physiological acute exercise-induced
fatigue (5 £10 RM leg press) changes after two loading
protocols with the same relative intensity (%) (5 £
10 RMRel) and the same absolute load (kg) (5 £10 RMAbs)
as in pretraining in men (n= 12). Exercise-induced neuro-
muscular (maximal strength and muscle power output),
acute cytokine and hormonal adaptations (i.e., total and free
testosterone, cortisol, growth hormone (GH), insulin-like
growth factor-1 (IGF-1), IGF binding protein-3 (IGFBP-3),
interleukin-1 receptor antagonist (IL-1ra), IL-1, IL-6, and
IL-10 and metabolic responses (i.e., blood lactate) were
measured before and after exercise. The resistance training
induced similar acute responses in serum cortisol concen-
tration but increased responses in anabolic hormones of FT
and GH, as well as inXammation-responsive cytokine IL-6
and the anti-inXammatory cytokine IL-10, when the same
relative load was used. This response was balanced by a
higher release of pro-inXammatory cytokines IL-1 and
cytokine inhibitors (IL-1ra) when both the same relative
and absolute load was used after training. This enhanced
hormonal and cytokine response to strength exercise at a
given relative exercise intensity after strength training
occurred with greater accumulated fatigue and metabolic
demand (i.e., blood lactate accumulation). The magnitude
of metabolic demand or the fatigue experienced during the
resistance exercise session inXuences the hormonal and
cytokine response patterns. Similar relative intensities may
elicit not only higher exercise-induced fatigue but also an
increased acute hormonal and cytokine response during the
initial phase of a resistance training period.
Keywords Serum hormones · Cytokines ·
Resistance training · Muscle power
M. Izquierdo (&) · J. Ibañez · I. Navarro-Amezqueta ·
M. González-Izal · E. M. Gorostiaga
Studies, Research and Sport Medicine Center,
Government of Navarra, C/Sangüesa 34,
31005 Pamplona, Navarra, Spain
e-mail: mikel.izquierdo@ceimd.org
J. A. L. Calbet
Department of Physical Education,
University of Las Palmas of Gran Canaria,
Las Palmas de Gran Canaria, Spain
F. Idoate
Departament of Radiology,
Clinic of San Miguel, Pamplona, Spain
K. Häkkinen
Department of Biology of Physical Activity,
University of Jyväskylä, Jyväskylä, Finland
W. J. Kraemer
Human Performance Laboratory, Department of Kinesiology,
University of Connecticut, Storrs, CT 06269-1110, USA
W. J. Kraemer
Human Performance Laboratory,
Department of Physiology and Neurobiology,
University of Connecticut, Storrs, CT 06269-1110, USA
M. Palacios-Sarrasqueta
Biochemistry Unit, Hospital of Navarre, Pamplona, Spain
M. Almar
Institute of Biomedicine, University of León, 24071 León, Spain
Eur J Appl Physiol
123
Introduction
Heavy resistance exercise protocols have been shown to
elicit signiWcant acute hormonal responses that are part of
an integrated system of signaling to a multitude of target
cells. Such complex interactions may be critical to the
support and mediation of physiological adaptations to
resistance training (Hakkinen et al. 1998; Kraemer and
Ratamess 2005; McCall et al. 1999; Staron et al. 1994).
Dramatic physiological changes in muscle have been dem-
onstrated in the Wrst several resistance training workouts. In
a study by Staron et al. (1994), it was demonstrated that
within four workouts myosin ATPase started to shift to the
Type IIa isoform. While changes in the muscle Wber charac-
teristics have been associated with the circulatory concen-
trations, how testosterone and cortisol help to mediate such
protein adaptations remains unclear. The direct interactions
in the circulation with immune cells and cytokine releases
might be a primary target of such hormones. Thus, new
insights into the physiological adjustments taking place
may be gained by the further elucidation of such relation-
ships and temporal changes in cytokine and immune regu-
lation with anabolic and catabolic hormones during a
resistance training program (Kraemer and Ratamess 2005;
Peake et al. 2005).
Resistance exercise may cause myoWbrillar disruption,
especially after a fatiguing task, and trigger an inXamma-
tory response. In fact, cytokines are increased in the circu-
lation in response to intense concentric and eccentric
muscle contractions. They are proposed to play a role in tis-
sue remodeling, especially in response to muscle damage
(Pedersen et al. 2001, 2003; Steensberg et al. 2000). While
the immune response to aerobic training and susceptibility
to upper respiratory tract infections has received great
attention (Pedersen et al. 2001, 2003), much less is known
about the acute changes in circulating cytokines induced by
a single resistance training session or following a number
of training sessions (Pedersen et al. 2001, 2003; Steensberg
et al. 2000).
Prior studies have demonstrated that acute resistance
exercise transiently elevates circulating concentrations of
anabolic/catabolic hormones (i.e., testosterone, growth hor-
mone (GH), cortisol), and cytokines including interleukin
(IL) IL-1, IL-6, IL-1, IL-1 receptor antagonist (IL-1ra)
and IL-10 (Evans et al. 1986; MacIntyre et al. 2001;
Takarada et al. 2000). The greatest testosterone and cortisol
responses are observed during large muscle-mass exercise
and high-volume sessions performed at moderate to high
intensity, using short resting intervals between sets
(Kraemer and Ratamess 2005). With the controversy of the
role of testosterone and cortisol in circulation, one of its
primary targets might be the modulating activities of
immune cells in circulation. In vitro evidence demonstrates
that testosterone may suppress the expression of the proin-
Xammatory cytokines TNF , IL-1ß, and IL-6 (D’Agostino
et al. 1999) and potentiate the expression of the antiinXam-
matory cytokine IL-10 (Bebo et al. 1999). Furthermore,
cytokine IL-6 release in response to exercise may also be
partly responsible for increases plasma cortisol in a similar
manner (Steensberg 2003). However, the extent to which
there is an interaction between the endocrine and cytokine
responses in trained and untrained individuals remains to be
elucidated.
It is a well-established principle of training that progres-
sive overload (e.g., increasing volume and intensity) is
necessary to increase muscular strength and that for
adaptations to occur, a stimulus exceeding a previous stim-
ulus needs to be applied during a resistance training pro-
gram (Gonzalez-Badillo et al. 2006; Izquierdo et al. 2006;
Kraemer and Ratamess 2005). Conceptually, this would
suggest that the stress-related overload in the context of a
short-term resistance training cycle may be progressively
increased in each training session (Gonzalez-Badillo et al.
2006; Izquierdo et al. 2006). However, the role played by
the absolute load and the relative load in the acute hormone
and cytokine response to resistance training remains to be
determined. Therefore, the purposes of the present study
were (1) to determine if the hormone and cytokine
responses to a standardized training session are augmented
after 7 weeks of heavy resistance training, (2) and to deter-
mine the role played by the relative load of the training ses-
sion in the hormone and cytokine responses. As a result, we
determined the total and free testosterone, cortisol, GH,
insulin-like growth factor-1 (IGF-1), and IGF binding
protein-3 (IGFBP-3), interleukin-1 receptor antagonist (IL-
1ra), IL-1 , IL-6, and IL-10 plasma responses and we
related them to neuromuscular and metabolic (i.e., blood
lactate) changes, after two loading protocols performed
with the same relative intensity (% of 1 RM) as well as the
same absolute load (kg) before and after training.
Methods
Experimental design
A longitudinal randomized research design was used during
the early phase of heavy resistance training (7 weeks) to
compare the neuromuscular and hormonal responses, and
their recovery proWles elicited by two loading protocols
with the same relative load (%) and the same absolute load
(kg) as in pretraining. The experimental design consisted of
three acute heavy-resistance exercise protocols (AHREP).
One of them was performed in pretraining (5 £10 RM leg
press) and the other two after the 7-week experimental
resistance training period. Baseline testing was completed
Eur J Appl Physiol
123
during the Wrst 3 weeks of the study preceding the start of
the training program. The two AHREP sessions performed
after training were randomized and separated by 7 days.
They were performed with the same relative load (%) (i.e.,
new 10 RM load) and the same absolute load (kg) as in pre-
training (see Fig. 1). The volunteers were familiarized with
the testing procedures about 2 weeks before the AHREP
session. After a thorough familiarization session, the sub-
jects participated in a control testing day 1 week before the
AHREP to determine one repetition maximum (1 RM),
maximal voluntary contraction (MVC), muscle power, and
the load corresponding to 10 RM (Fig. 1).
Immediately before each AHREP (pre-exercise) session
each subject’s 1 RM and MVC were determined. Muscle
power was assessed with the load corresponding to pre-
exercise 10 RM (i.e., control). After each AHREP, i.e., in
the fatigued state, the MVC and muscle power with the
load corresponding to 10 RM was performed immediately
post-exercise (post 0) (Fig. 1) (Izquierdo et al. 2009). Each
subject was required to have a 3-day food diary record for
the days prior to testing and repeat the same diet before
each main trial in order to minimize the variation in physio-
logical responses. In addition, subjects did not ingest any
food except water for 1 h prior to the experimental proce-
dures. In order to exclude any residual eVects of previous
exercise on the experimental treatment, the subjects were
also required to refrain from strenuous exercise and the
consumption alcohol, tobacco or caVeine 48 h before and
between the testing sessions.
Subjects
Twelve physically active healthy men volunteered to
participate in the study. The subjects’ mean (§SD) age,
height, body mass, and percentage of body fat were 33
(§4.4) years, 1.77 (§0.06) months, 72.4 (§6.9) kg and
9.2% (§2.5), respectively. In order to document the initial
physiologic changes we used subjects with no weight
training experience. This enabled the observation of the
acute physiologic changes that took place in a resistance
training program. Each subject gave his written informed
consent to participate after the risks involved in the study
were explained in detail. The experimental procedures were
approved by the Institutional Review Committee of the
Instituto Navarro del Deporte and were in accordance with
the Declaration of Helsinki. Before inclusion in the study,
all subjects were medically screened by a physician and
were seen to be free from any orthopedic, electrocardio-
graphic, endocrinal, or medical problems that would
contraindicate their participation or inXuence the results of
the investigation. None of them was taking exogenous
anabolic-androgenic steroids, drugs, medication, or dietary
supplements with potential eVects on physical performance.
Acute heavy resistance loading protocols
The experimental design comprised the examination of
resistance training-induced adaptations on the acute neuro-
muscular, hormonal, and cytokine responses with the same
absolute (kilogram) and relative load (% of 1 RM). Before
training, the AHREP consisted of Wve sets with the maxi-
mum load possible to achieve ten repetitions (10 RM) in
leg press with 120 s of rest between the sets. After training
each subject performed the two AHREP in random and bal-
anced order separated by 7 days: one with the same relative
load (5 £10 RMRel) and the other with the same absolute
load (5 £10Abs) as in pretraining testing. If the subject
failed to reach the tenth repetition during the 5 £10 RMRel,
Fig. 1 Acute heavy resistance
protocol design (a) and
longitudinal experimental
design (b)
Eur J Appl Physiol
123
the load was reduced and the exercise resumed allowing the
completion of ten repetitions on each set. This maneuver
was repeated as many times as necessary so that each
set always consisted of ten repetitions. For comparison pur-
poses, the 5 £10 RMAbs AHREP performed after the resis-
tance training period was carried out with the same absolute
loads used in pretraining testing.
A bilateral leg press exercise machine (i.e., leg press
action in a sitting position) (Technogym, Gambettola, Italy)
was used for all trials. The seat was individually adjusted to
minimize displacement between the lower back and the
backrest during muscular force exertion. Strong verbal
encouragement was given to all subjects to motivate them
to perform each test action as maximally and as rapidly as
possible.
Maximal strength and muscle power output
1 RM (i.e., the heaviest load that could be lifted only once
using the correct technique) was determined for the leg
press exercise (Technogym, Gambettola, Italy). The subject
was in a seated position so that the knee angle was 90º.
Three to four subsequent attempts were made to determine
1 RM. The rest between maximal attempts was always
2min.
Maximal isometric force was also measured on a modi-
Wed leg press exercise machine (Technogym, Gambettola,
Italy) at knee and hip angles of 90º and 45º, respectively.
The exercise machine incorporated several force transduc-
ers on a foot platform located below the subject’s feet. The
strain gauges recorded the applied force (N) to an accuracy
of 1 N at 1,000 HZ.
Muscle power output of the leg extensor muscles was
measured during the concentric phase of leg press using the
load corresponding to 10 RM. An optical encoder
(Computer Optical Products Inc, California, USA) was
attached to weight plates to record the position and direc-
tion of the displacement to an accuracy of 0.2 mm at
1,000 Hz. Customized software was used to calculate range
of motion, peak power output, and average velocity for
each repetition. Subjects were instructed to displace the
weights as fast as possible. Two testing trials were recorded
and the best trial was taken for further analysis. The test–
retest intraclass correlation coeYcients for all strength and
power variables were greater than 0.95 and the coeYcients
of variation (CV) ranged from 0.9 to 2.1%.
Muscle cross-sectional area (CSA) and anthropometry
The muscle CSA of the left quadriceps femoris (QF) was
assessed before and after the 7-week resistance training
period using magnetic resonance imaging (MRI) (SIE-
MENS Magnetom Impact Expert, 1 T). Once the subject
was positioned within the magnet, the thighs of both legs
were kept parallel to the MRI table, and the feet were
strapped together to prevent rotation. The length of the
femur (Lf), taken as the distance from the intercondilar
notch of the femur to the superior boundary of the femoral
head, was measured on a coronal plane. CSA computation
was carried out on the QF as a whole. Body mass and per-
cent body fat (estimated from the thickness of seven skin-
fold sites) were taken before and after each training period
(Jackson and Pollock 1978).
Resistance training program
A trained researcher supervised each workout session
carefully so that exercise prescriptions were correctly
administered during each training session (e.g., number
of repetitions, rest and velocity of movement). Compli-
ance with the study was 100% of the programmed
sessions.
Subjects trained two times per week for 7 weeks to
perform dynamic resistance exercises from 45 to 60 min
per session. A minimum of 2 days elapsed between two
consecutive training sessions. During the whole training
period, the core exercises were parallel-squat and bench
press in addition to supplementary strengthening exercises
for selected muscle groups (leg press, leg extension, shoul-
der press, lateral pull-down, abdominal crunch, trunk exten-
sion, and standing leg curl). The resistance training
consisted of a nonlinear undulating, multi-set, multi-exer-
cise, progressive program performed two times per week.
The daily workouts were alternated by varying the resis-
tance (intensity), and the volume (sets £repetitions £ load)
over the week. On Tuesday, the sets were performed at
12–15 RM with 2 min rest between sets. Finally, on Thursday
the sets were performed at the 10 RM intensity with 2 min
rest between sets. Three to Wve sets were performed during
the training program. The assigned training intensities were
gradually increased during the 7-week training period using
a repetition maximum approach.
Blood collection and analysis
The subjects visited the laboratory and rested for 30 min
before the Wrst blood collection. During the loading session,
blood samples were drawn from an antecubital forearm
vein using a 20-gauge needle and vacutainers® for the
determination of serum total an free testosterone, cortisol,
GH, insulin-like growth factor-1 (IGF-1), and IGF binding
protein-3 (IGFBP-3), interleukin-1 receptor antagonist (IL-
1ra), IL-1, IL-6, and IL-10 concentrations pre-exercise,
after the third set (mid-exercise), immediately after (post),
and after 15 min (post-15 min) and 45 min (post-45 min)
after the loadings. During the control day, i.e., without
Eur J Appl Physiol
123
exercise, two blood samples were also drawn within 30 min
at the same time of day when the loading protocols were
carried out. Blood samples were obtained at diVerent times
of the day from subjects but at the same time of day for
each subject in each loading protocol before and after the
experimental training period, to minimize the inXuence of
any diurnal variation.
Whole blood was centrifuged at 3,000 rpm (4°C) for
15 min and the resultant serum was then removed and
stored at ¡20°C until subsequent analysis. All samples
were assayed in duplicate and were decoded only after the
analyses were completed (i.e., blinded analysis procedure).
Circulating concentrations of total testosterone, cortisol,
GH, IGF-1, IGFBP-3, IL-1ra, IL-1, IL-6, and IL-10 were
determined using commercially available enzyme-linked
immunosorbent assay (ELISA) kits (DRG Diagnostics,
DRG Instruments GmbH, Marburg, Germany). Because no
signiWcant diVerences in plasma volume changes were
observed between the loading conditions before and after
training, hormonal concentrations were not corrected for
plasma volume changes (Dill and Costill 1974). Samples
were only thawed once before the analysis for all proce-
dures,
Capillary blood samples for the determination of blood
lactate concentrations were obtained from a hyperemized
earlobe pre-exercise, as well as after exercise to determine
the peak blood lactate concentration post exercise (i.e.,
post-exercise (post 0), and 3, 5, 10, 15 min into the recov-
ery period). Samples for whole blood lactate determination
(100 l) were deproteinized, placed in a preservative tube
(YSI 2315 Blood Lactate Preservative Kit), stored at 4°C,
and analyzed (YSI 1500) within 5 days of completing the
test. The blood lactate analyzer was calibrated after every
Wfth blood sample dose with three known controls (5, 15,
and 30 mmol l¡1).
Statistical analyses
The training-related eVects were assessed using a two-
way ANOVA with repeated measures (time £protocol).
When a signiWcant F value was achieved, Bonferroni
post hoc procedures were performed to locate the pair-
wise diVerences between the means. Statistical compari-
son during the control period (from week –3 to week 0)
was done by Student’s paired t test. Selected absolute
and relative changes (e.g., maximal strength, muscle
power output, acute cytokine and hormonal adaptations)
were analyzed via one-way analysis of variance. Statisti-
cal power calculations for this study ranged from 0.75 to
0.80. The P·0.05 criterion was used to establish statis-
tical signiWcance. Values are reported as mean values §
and standard deviations (SDs).
Results
Anthropometry and muscle CSA
After the 7-week training period, a signiWcant increase was
observed in body mass (from 72.4 §6.9 to 73.4 §6.2 kg,
P< 0.05), and quadriceps CSA (from 130.1 §10.6 to
135.7 §12.2 cm2, P< 0.001), whereas no signiWcant
changes were observed in body fat.
Maximal bilateral isometric, 1 RM dynamic strength
and muscle power output
Maximal strength and muscle power output remained unal-
tered during the 3-week control period (from week ¡3 to
week 0). During the 7-week training period, signiWcant
increases of 10.8 §1.3% (P< 0.05) were recorded in max-
imal isometric force (from 1557 §211 to 1772.7 §304 N)
and 19.7 §4.7% in 1 RM (from 190.6 §30.2 to 237.9 §
38.8 kg).
After the 7-week training period, peak power output
with the same absolute load as in pretraining increased by
16.2 §12.8% (from 1163.2 §239.9 to 1414.4 §372.0 W,
P< 0.01), whereas no signiWcant changes were observed in
peak power output with the same relative load used in pre-
training (from 1163 §239 to 1159 §320 W).
Acute heavy 10 RM resistance loading
After the 7-week training period, the initial load of
the 5 £10Rel loading protocol was increased from
160.2 §26.3 to 198.9 §33.9 kg (P< 0.05). In pretrain-
ing, the load used during the 10 RM loading protocol
corresponded to 84.1 §4.8% of 1 RM (ranging from
75.1 to 90.5%) similar to that of 83.7 §4.8% of 1 RM
(ranging from 74.9 to 91.1%) used in posttraining. After
training, total work (sets £reps £load) performed with
the same relative load (5 £10Rel loading) was increased
by 15.5 §6.6% compared with that used in pretraining
(from 7515.7 §1040.1 to 8939.6 §1340.6 kg, P< 0.05).
After training, the load used during the 5 £10 RMAbs
represented 67.6 §5.7% of the posttraining 1 RM. Total
work (sets £reps £load) performed with the same
absolute load (5 £10 RMAbs loading) was similar in
pre and posttraining (7515.7 §1040.1 kg and 7521 §
1039.1 kg, respectively). After training, the relative
decrease (%) of the load during the 5 £10Rel protocol
was higher (P< 0.05) for the second, fourth, and Wfth
sets compared with that recorded in pretraining. For
comparison purposes, after training the absolute
decrease of the load during the 5 £10Abs loading proto-
col was matched to that recorded in pretraining.
Eur J Appl Physiol
123
Acute maximal isometric and muscle power output
responses to training
Maximal isometric force immediately after the 5 £10Rel
loading was decreased by 23.4 §11.7 and 34.2 §15.8%
(both P< 0.05), but with a signiWcantly greater exercise-
induced loss of MVC after training (pre vs. posttraining)
(Fig. 2a). Training attenuated the losses in MVC elicited by
the 5 £10Abs loading protocol (11.4%) compared to those
elicited by the 5 £10Rel loading protocol (Fig. 2a).
Peak power output decreased in a similar manner
(P< 0.05) immediately after the 5 £10Rel loading proto-
cols in both pretraining and posttraining (58.4 §14.5 and
62.3 §14.4%, respectively) (Fig. 2b). After training, sig-
niWcant decreases were observed in peak power output
immediately post-exercise in the 5 £10Abs loading
protocol (20.3%) (Fig. 2b). The 5 £10Abs loading protocol
elicited signiWcant lower reductions in peak power output
after training than both 5 £10Rel loading protocols.
Blood lactate concentrations
After training, post exercise peak blood lactate was signiW-
cantly greater in the 5 £10rel compared with that observed
in the 5 £10 pretraining protocol. The blood lactate
response was lower (P< 0.05) during the whole loading
period in the 5 £10Abs compared with the response
observed in the 5 £10Rel (Fig. 3).
Acute hormonal responses to training
Basal hormonal levels remained unaltered during the
3-week control period (from week ¡3 to week 0). There were
no signiWcant changes between the three control blood
Fi
g.
2Ab
so
l
ute an
d
re
l
at
i
ve
changes in maximal isometric
force (a) and peak power output
(b), pre and post loading before
at pretraining (5 £10 pretrain-
ing) and after 7 weeks of period-
ized strength training with both
the same relative (5 £10Rel) and
the same absolute load
(5 £10Abs) as pretraining. Filled
triangle signiWcant diVerence
(P< 0.05) compared to the
corresponding pre-exercise
value, for each protocol.
#P< 0.05 signiWcant diVerences
between 5 £10Abs post training
and the other two protocols.
§P< 0.05 signiWcant diVerences
between 5 £10 pretraining and
5£10Rel post-training
Eur J Appl Physiol
123
samples drawn within 30 min on the control day (i.e., with-
out exercise) at the same time at which each subject had
performed the two loading protocols before and after training.
Serum total and free testosterone concentrations
increased signiWcantly after the loading both before and
after the strength training period, but decreased to the pre-
exercise value at 45 min post-exercise. Acute exercise-
induced serum total testosterone responses to 5 £10Abs or
5£10Rel loading protocols were similar in pre and post-
training (Fig. 4a). After training, the mean acute free testos-
terone response was greater (P< 0.05, mid exercise and
post exercise) in 5 £10Rel compared with that observed in
the 5 £10Abs protocol and the 5 £10Rel at pretraining
(Fig. 4b).
Serum cortisol concentration increased signiWcantly 15
and 45 min after 5 £10Rel pretraining and 5 £10Rel post-
training (Fig. 5), the increment being similar in both condi-
tions. Acute cortisol responses were signiWcantly lower
during the whole loading and recovery period in 5 £10Abs
compared with the responses observed in both 5 £10Rel
loading protocols (pre and posttraining) (Fig. 5).
Serum GH concentration was signiWcantly increased
post-exercise as well as after 15 and 45 min during the
recovery period. This increase was similar during both rela-
tive loading sessions performed before (5 £10Re pretrain-
ing) and after the training period (5 £10Rel posttraining).
After training, no signiWcant changes were observed in any
Fig. 3 Blood lactate concentrations (Mmol L¡1) pre-exercise and
peak value at pretraining (5 £10 pretraining) and after 7 weeks o
f
periodized strength training with both the same relative (5 £10Rel) and
the same absolute load (5 £10Abs) as pretraining. Filled triangle
signiWcant diVerences (P< 0.05) from the corresponding pre-exercise
value. #SigniWcant diVerences (P< 0.05) with the other two protocols
Fig. 4 Serum total testosterone
(a) and free testosterone (b) con-
centrations before, pre-, mid-,
and post-exercise and during
recovery at pretraining (5 £10
pretraining) and after 7 weeks of
periodized streng th training with
both the same relative
(5 £10Rel) and the same abso-
lute load (5 £10Abs) as pretrain-
ing. Filled triangle signiWcant
diVerence (P< 0.05) compared
to the corresponding pre-exer-
cise value, for each protocol.
aSigniWcant diVerences
(P< 0.05) from the correspond-
ing post 0 value, for each proto-
col. bSigniWcant diVerences
(P< 0.05) from the correspond-
ing post 3 min value, for each
protocol. cSigniWcant diVerences
(P< 0.05) from the correspond-
ing post 5 min value, for each
protocol. #P< 0.05 signiWcant
diVerences between 5 £10Abs
post training and the other two
protocols
Eur J Appl Physiol
123
loading or recovery points of the loading session performed
with the same absolute load as in pretraining (5 £10Abs
protocol). After the training period, acute GH response was
signiWcantly greater in the 5 £10Rel protocol, compared
with those recorded during the 5 £10Rel pretraining (i.e.,
post exercise and post 15 min) and 5 £10Abs posttraining
loading sessions (i.e., post exercise, post 15 min and
45 min). Furthermore, the acute GH responses were signiW-
cantly lower after the 5 £10Abs protocol (i.e., post exercise,
15 and 45 min post-exercise) compared with the responses
observed during the 5 £10Rel loading sessions (pre and
posttraining) (Fig. 6).
No signiWcant changes were observed in the acute IGF-1
and IGFBP-3 responses at any point (P< 0.05, mid-exercise,
post-exercise, and 45 min after recovery) during the loading
or recovery period during both pretraining and posttraining
loading sessions (5 £10Abs or 5 £10Rel). No signiWcant
diVerences were observed in the acute IGF-1 and IGFBP-3
responses, regardless of whether 5 £10Abs or 5 £10Rel pro-
tocols were performed after the training period.
Cytokines
After the training period, the acute IL-1 response was sig-
niWcantly higher during the whole loading and recovery
period in both 5 £10Abs and 5 £10Rel protocols, compared
with the acute response recorded during the 5 £10 RM
protocol in pretraining.
Fig. 5 Serum cortisol concentration before, pre-, mid- and post-exer-
cise and during recovery at pretraining (5 £10 pretraining) and after
7 weeks of periodized strength training with both the same relative
(5 £10Rel) and the same absolute load (5 £10Abs) as pretraining.
Filled triangle signiWcant diVerence (P< 0.05) compared with the
corresponding pre-exercise value, for each protocol. aSigniWcant diVer-
ences (P< 0.05) from the corresponding post 0 value, for each proto-
col. bSigniWcant diVerences (P< 0.05) from the corresponding post
3 min value, for each protocol. #P< 0.05 signiWcant diVerences
between 5 £10Abs post training and the other two protocols
Fig. 6 Serum growth hormone concentration before, pre-, mid-, and
post-exercise and during recovery at pretraining (5 £10 pretraining)
and after 7 weeks of periodized strength training with both the same
relative (5 £10Rel) and the same absolute load (5 £10Abs) as pretrain-
ing. *SigniWcant diVerence (P< 0.05) compared to the corresponding
before value, for each protocol. Filled triangle signiWcant diVerence
(P< 0.05) compared to the corresponding pre-exercise value, for each
protocol. aSigniWcant diVerences (P< 0.05) from the corresponding
post 0 value, for each protocol. #P< 0.05 signiWcant diVerences
between 5 £10Abs post training and the other two protocols
Eur J Appl Physiol
123
IL-1ra concentrations signiWcantly increased at mid- and
post-exercise point, but decreased to the pre-exercise value
at 15 and 45 min after recovery during the 5 £10Rel pre-
training loading protocol. After training, no signiWcant
changes were observed IL-1 and IL-1ra (P< 0.05; for IL-
1ra at Post 0 min) concentrations in both relative loading
protocols (Fig. 7a, b).
Serum IL-6 concentration signiWcantly increased at
45 min post-exercise in both pretraining and posttraining
5£10Rel protocols. After the training period, the acute IL-
6 response in the 5 £10Rel protocol in the 45-min recovery
period was signiWcantly greater compared with the acute
responses recorded during 5 £10 pretraining and posttrain-
ing 5 £10Abs loading conditions (Fig. 8a).
No signiWcant changes were observed in acute serum IL-
10 concentrations at any loading or recovery point of the
loading sessions performed in pretraining and posttraining
with the same absolute load (5 £10Abs protocol). After
training, acute serum IL-10 concentration signiWcantly
increased at mid- and post-exercise, as well as after 15 and
45 min during the recovery period in the 5 £10Rel proto-
col. After the training period, the acute IL-10 response in
the 5 £10Rel protocol was signiWcantly greater in mid- and
post-exercise as well as during the 15 and the 45 min recov-
ery period, compared with the acute responses recorded
during pretraining 5 £10 RM and posttraining 5 £10Abs
loading conditions (Fig. 8b).
Discussion
The mains Wndings of this study were that 7 weeks of heavy
resistance training induced (1) greater magnitude of acute
exercise-induced MVC loss than in pretraining, when exer-
cising with the same relative intensity, (2) similar acute
responses in serum cortisol concentration but increased free
testosterone and GH responses, to the same relative load,
(3) greater IL-6 (pro-inXammatory) and IL-10 (anti-inXam-
matory) responses after exercising with the same relative
load, as well as (4) greater release of pro-inXammatory
cytokines IL-1 and IL1-ra after exercising either at the
same relative or absolute load.
EVects on fatigue
The short-term resistance training period led to higher
accumulated fatigue and metabolic demand (i.e., blood lac-
tate accumulation) after multiple sets of dynamic fatiguing
contractions with the same relative load as in pretraining.
As has been previously reported (Izquierdo et al. 2009),
after a short-term strength training period, when the relative
intensity of the fatiguing dynamic protocol was kept the
same, the magnitude of exercise-induced loss of functional
capacity (power and MVC) was greater than that observed
before training, but lower fatigue occurred when the same
absolute load was used. Previous studies have demonstrated
Fig. 7 Interleukins IL-1 (a)
and IL-ra (b) serum concentra-
tions before, pre-, mid- and post-
exercise and during recovery at
pretraining (5 £10 pretraining)
and after 7 weeks of periodized
strength training with both the
same relativ e (5 £10Rel) and the
same absolute load (5 £10Abs)
as pretraining. *SigniWcant
diVerence (P< 0.05) compared
to the corresponding before
value, for each protocol. Filled
triangle signiWcant diVerence
(P< 0.05) compared to the cor-
responding pre-exercise value,
for each protocol. #P<0.05
signiWcant diVerences between
5£10Abs post training and the
other two protocols
Eur J Appl Physiol
123
similar decreases in maximal isometric strength in physi-
cally active and strength-trained male athletes (Ahtiainen
et al. 2003), when the relative intensity of the loading was
kept the same before and after a long-term strength training
period (21 weeks), whereas in other studies the magnitude
of exercise-induced loss in maximal strength or muscle
power was not reported (Hickson et al. 1994; Kraemer et al.
1998; Kraemer et al. 1999; McCall et al. 1999). Further-
more, as expected, resistance training resulted in a remark-
able increase in exercise performance (i.e., reduced
fatigability) as shown by the attenuation of the degree of
fatigue elicited by the same absolute load after training.
Hormonal responses
A limited number of studies have examined the eVects of
resistance training on acute exercise-induced hormonal
responses with the same relative and absolute intensity as in
pretraining. The increased free testosterone and GH
response to acute exercise with the same relative load after
progressive heavy resistance training is in accordance with
other studies (Craig et al. 1989; Kraemer et al. 1998). Craig
et al. (1989) reported that young men increased GH con-
centration up to Wvefold in response to an acute bout of
resistance exercise and this increased up to sixfold after
training, whereas the acute total testosterone response to a
single lifting session was the same before and after training.
Kraemer et al. (1998) reported that untrained men are able
to develop an acute exercise-induced increase in testoster-
one, but a similar GH response in pre and posttraining.
However, other studies did not Wnd any signiWcant changes
in the proWles of acute hormonal responses to resistance
exercise due to long-term strength training in adult men
(Ahtiainen et al. 2005; Hickson et al. 1994; Kraemer et al.
1999; McCall et al. 1999). Comparison of our results with
other studies is diYcult because the magnitude of exercise-
induced loss in maximal strength or muscle power has not
been reported systematically.
To the author’s knowledge only Ahtiainen et al. (2003)
reported similar exercise-induced decreases in maximal
isometric strength pre and posttraining after the 21-week
training period. This was accompanied by no signiWcant
diVerences in acute cortisol, total and free testosterone
responses between strength-trained and untrained men
between the loading sessions, but an attenuated acute GH
response in the male strength-athlete group. Resistance
training may also have led to an overall reduction (Kraemer
et al. 1999; Staron et al. 1994) or similar (Ahtiainen et al.
2003; Ahtiainen et al. 2005) cortisol responses to exercise
loading in men. In the present study, after the 7-week
strength training period, when the relative intensity of the
fatiguing dynamic protocol was kept the same, the acute
Fig. 8 Interleukins IL-6 (a) and
IL-10 (b) serum concentrations
before, pre-, mid- and post-exer-
cise and during recovery at pre-
training (5 £10 pretraining) and
after 7 weeks of periodized
strength training with both the
same relativ e (5 £10Rel) and the
same absolute load (5 £10Abs)
as pretraining. *SigniWcant
diVerence (P< 0.05) compared
with the corresponding before
value, for each protocol. Filled
triangle signiWcant diVerence
(P< 0.05) compared with the
corresponding pre-exercise val-
ue for each protocol. #P<0.05
signiWcant diVerences between
5£10Abs post training, and the
other two protocols
Eur J Appl Physiol
123
cortisol response to resistance exercise was similar to that
observed before training. These results may indicate that
diVerences in GH and testosterone responses to acute exer-
cise after training may not only be sensitive to the relative
intensity but also to other factors related to the higher abso-
lute intensity of the exercise after training, e.g., greater met-
abolic demand. It maybe that this metabolic demand plays a
primary role in these circulating hormonal concentrations.
A unique but expected Wnding of this study was fewer
signs of acute exercise-induced fatigue (i.e., reduced fatiga-
bility) in the protocol in posttraining with the same absolute
load as in pretraining, accompanied by an attenuated
release in the cortisol and GH response but interestingly
similar total and free testosterone acute responses after
training. This could be due to the decreased stress response
and/or decreased hormone production. A typical response
to resistance training is a reduction of the amount of muscle
mass needed to perform a given dynamic task, as demon-
strated using NMR and EMG measurements (Lewis et al.
1984; Ploutz et al. 1994). Thus, the same amount of
strength and power can be developed after training using
fewer muscle Wbers with lesser accumulation of fatigue.
These two eVects can only be explained by changes in neu-
ral activity combined with local muscular functional and
structural changes. Strength training leads to improvements
in neuromuscular eYciency (i.e., the relationship between
EMG and mechanical power output) (Behm and St-Pierre
1998), muscle mass (Aagaard et al. 2001; Hakkinen et al.
1985), selective hypertrophy of IIA muscle Wbers (Staron
et al. 1994) and enhanced muscle metabolism (i.e.,
increased activity of creatine kinase (CK), glycolytic
enzymes, e.g., phosphofructokinase (PFK), decreases in
lactate accumulation, and increases in muscle buVering
capacity) (Hellsten et al. 1996; McKenna et al. 1993; Mohr
et al. 2007; Sahlin and Henriksson 1984). Changes of this
nature could have occurred in our subjects as a result of
resistance training and hence contribute to the explanation
of reduced fatigability and attenuated acute hormonal
response to acute loading with the same absolute load as in
pretraining. This Wnding implies that it may be necessary to
adjust the load to achieve similar acute hormonal responses
after a short-term training period. Therefore, similar rela-
tive intensity may induce not only higher exercise-induced
fatigue but also increased acute hormonal responses during
the initial phase of the resistance training period.
Cytokine responses
Resistance exercise is known to cause myoWbrillar disrup-
tion, especially during eccentric muscle actions (Bruunsgaard
et al. 1997; Gibala et al. 2000). This disruption results in an
inXammatory response, modulated by cytokines (Pedersen
et al. 2001; Pedersen et al. 2003). Interleukin-6 (IL-6) is
locally produced by growing myoWbers and acts as an
essential regulator of satellite cell (muscle stem cell)-medi-
ated hypertrophic muscle growth (Hiscock et al. 2004; Kel-
ler et al. 2001; Penkowa et al. 2003; Serrano et al. 2008;
Vierck et al. 2000). Further, it appears that cytokines may
also play a role in the repair and remodeling process of
muscle (Pedersen et al. 2001, 2003; Steensberg et al. 2000).
Our study shows that greater exercise-induced levels of
IL-6 are only elicited in the training sessions in the initial
phase of heavy resistance training when the sessions are
carried out with the same relative loads. In accordance with
this, IL-6 was shown to be signiWcantly high for up to
48 hours after heavy total body eccentric resistance exer-
cise, together with closely matched delayed onset muscle
soreness (Smith et al. 2000; Suzuki et al. 2002). An earlier
isokinetic eccentric-only training study also reported
increases in IL-6 post exercise, but there were no signiWcant
diVerences between pre and posttraining levels (Croisier
et al. 1999). IL-6 was elevated for up to 1 day after pro-
longed eccentric leg extension exercise (300 repetitions),
and these elevations were signiWcantly correlated to
delayed onset muscle soreness (MacIntyre et al. 2001).
Even very light eccentric exercise (20% or 1 RM leg exten-
sion) coupled with circulatory occlusion resulted in
increased IL-6 response up to 3 h post exercise (Takarada
et al. 2000).
Furthermore, a higher release of pro-inXammatory cyto-
kine IL-1 in the 5 £10Abs or 5 £10Rel acute loading pro-
tocols was also reported after training in the present study.
Previous studies reported reduced (Smith et al. 2000) or
increased (Evans et al. 1986) levels of IL-1 associated
with muscle damage following eccentric exercise. The dis-
crepancies between these studies may partly result from
diVerences in the loading regimes studied, and to the fact
that IL-1 undergoes a rapid clearance rate and local accu-
mulation at the trauma site (i.e., in this case, muscle).
Furthermore, in early studies such as this one, assay did not
diVerentiate between IL-1 and IL-1 (Evans et al. 1986).
However, the concomitant greater increase of IL-1ra in
response to resistance exercise (either at the same absolute
or relative intensity) could have blunted the biological
activities of IL-1 and IL-1 (Pedersen et al. 2001). IL-1ra
is up-regulated among others by IL-6 (Pedersen et al. 2001,
2003).
The present study also shows that short-term resistance
training only enhances the responsiveness of IL-10 to a
resistance exercise session when exercising at the same rel-
ative load. Previous studies have shown that IL-10 is
increased by catecholamines and in vivo IL-6 (Peake et al.
2005). IL-10 is increased after an acute bout of eccentric
elbow Xexor exercise; interestingly, this response is accen-
tuated when the same eccentric exercise is repeated 4 weeks
later (Hirose et al. 2004). The latter could contribute to an
Eur J Appl Physiol
123
attenuated inXammatory response to eccentric exercise and
explain the known protective eVect of a single session of
eccentric exercise on muscle structure and function. It
remains to be determined why and how the IL-10 and IL-6
responses to a resistance exercise session performed at the
same relative exercise intensity are accentuated after resis-
tance training. The interactions with circulating anabolic
and catabolic hormones may provide one distinct area of
research, linking these circulatory elements in an endo-
crine-immune cytokine cybernetic relationship. Our data
reXect such a pattern of interactions.
In summary, the present resistance training program
induced similar acute responses in serum cortisol concen-
tration but increased responses in anabolic hormones of
FT and GH, as well as inXammation responsive cytokine
IL-6 and the anti-inXammatory cytokine IL-10, when the
same relative load was used. This response was balanced
by a higher release of pro-inXammatory cytokines IL-1,
cytokine inhibitors (IL-1ra) when both the same relative
and absolute load was used after training. This enhanced
hormonal and cytokine response to resistance exercise at a
given relative exercise intensity after resistance training
occurred with greater accumulated fatigue and metabolic
demand (i.e., blood lactate accumulation). The magnitude
of metabolic demand or the fatigue experienced during
the resistance exercise session inXuences the hormonal
and cytokine response patterns. Similar relative intensi-
ties may elicit not only higher exercise-induced fatigue
but also an increased acute hormonal and cytokine
response during the initial phase of the resistance training
period.
Acknowledgments This study was supported by the Ministry of
Education (National Plan of R&D + i 2004-2007. Key Action “Sport
and Physical Activity” DEP2006-56076)
ConXict of interest statement The authors declare that they have no
conXict of interest relevant to the content of this manuscript.
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