ARTICLE
Auteur(s) : Chantal Jimenez, Bruno
Melin, Gustave Savourey, Jean-Claude Launay, Antonia Alonso,
Jacques Mathieu
Département des Facteurs Humains, Centre de Recherches du
Service de Santé des Armées, 24 avenue des Maquis du Grésivaudan,
38702 La Tronche Cedex, France
Many physiological and biological responses are different between
exercise-induced hyperthermia and passive hyperthermia. Stress
hormone responses are also different. Exercise increases
catecholamine release to ensure the inflow of oxygen and
metabolites towards the muscles [1-3], but not prolactin secretion
[4]. Passive hyperthermia increases plasma prolactin [4], but not
plasma catecholamines [2, 3]. Both challenges increase plasma
cortisol [1]. In addition, it is well known that physical exercise
affects the immune system. Intense exercise may be the origin of a
transient immunosuppression [5]. This phenomenon is amplified
during exercise in the heat. On the other hand, passive
hyperthermia could also act on the immune system. Few studies are
reported in the literature. Passive hyperthermia could enhance
pro-inflammatory cytokines synthesis as described by Downing [6]
and Ostberg [7], while Kappel [8] reported no effect. It seems that
hyperthermia, per se, has an effect on the immune response. But are
the effects of exercise-induced hyperthermia really different from
those of passive hyperthermia? Stress hormones have an influence on
the immune system [9-12]. Can they explain the differences in
immune responses between exercise and hyperthermia? Most studies on
immune responses during passive hyperthermia have been carried out
by immersion in warm water. The problem is that immersion has its
own effects on hormonal and hemodynamic responses, which are
independent of those of hyperthermia, in particular, catecholamine
levels are increased during immersion in warm water [13, 14]. It
appears preferable to study the effect of passive hyperthermia in a
climatic chamber. Therefore, the aim of this study was to compare
the effect of an increase in body temperature on immune and
hormonal responses during exercise versus during passive
hyperthermia in a climatic chamber, with the proviso of reproducing
the same evolution of body temperature during the two tests. In
addition, there are well-known tests to evaluate the functional
response of immunocompetent cells: the stimulation with
lipopolysaccharide (LPS) and phytohemagglutinin (PHA). LPS
stimulates primarily monocytes and B lymphocytes [15], whereas PHA
stimulates primarily T lymphocytes. This response causes the
production of several cytokines. We chose to investigate the
production INF-γ and TNF-α, which are the major pro-inflammatory
cytokines [16], and IL-10 which is one of the major
anti-inflammatory cytokines [16]. We also chose not to include
water or carbohydrate intake during the recovery period.
Methods
Eight subjects participated in the study. Age, weight and height
(mean ± sem) were 23 ± 1.5 years, 69.2 ± 2.8 kg and 172 ± 2 cm
respectively. The selection of the subjects was based on a normal
clinical investigation that comprised detail medical history,
physical examination and general blood screening. The subjects were
required to be regularly trained for endurance, and unaccustomed to
heat exposure. Procedures were carried out with the written
informed consent of the subjects. The protocol was approved by the
regional ethics committee (CCPPRB, Grenoble). Their physical
fitness was estimated from the maximal O2 uptake
(VO2 max), during a progressive treadmill test using a
breath-by-breath automated gas exchange system (MedGraphics CPX/D,
Medical Graphics Corporation, St Paul, MN, USA); the average result
was 52.0 ± 2.2 mL.min-1.kg-1. The
experiment took place in winter and spring.
Research design
A complete cross-over design was used in which each subject took
part in three trials. Each of these trials was separated by at
least 15 days. Three days before each trial the subjects were asked
to refrain from strenuous exercise and to drink at least 2 L
of water per day to ensure euhydration.
At the beginning of each experiment, the subjects arrived at the
laboratory at 8: 30, after a standard breakfast, and dressed
themselves in shorts. The subjects emptied their bladder, were
weighed and a polyethylene catheter (Angiocath 20GA 2in, Becton
Dickinson, Sandy, UT, USA) was inserted in an antecubital vein of
one arm. Throughout the experimental session, rectal temperature
(Tre) was recorded every min with thermistances (YSI series 400,
Yellow Spring, OH, USA). They were then asked to stay in a sitting
posture for the control (C) trial, in a standing posture for the
exercise trial (E), and in a semi-recumbent position for the
passive hyperthermia trial (PH) for 30 min to stabilize
hemodynamic conditions. At the end of the 30 min, a reference
blood sample (10 mL) was taken.
In the control trial (C), the subjects remained in a sitting
position for three hours in controlled thermal conditions (Tdb =
21-22°C, relative humidity (rH) = 35-45%). There were dressed in
shorts and a bathrobe in order to ensure thermoneutral
conditions.
In the exercise trial (E), the subjects exercised for two hours
on a treadmill, at 65% VO2 max in controlled thermal
conditions (Tdb = 21-22°C, rH = 35-45%). The wind speed was
modulated to ensure a rectal temperature = 38.5°C after 60 min
of exercise, and 39°C after 120 min of exercise. Following the
exercise, the subjects were dried, and stayed for 30 min at
Tdb = 21-22°C in a sitting position, and 30 min in a standing
position until the final blood sample was taken.
In the passive hyperthermia trial (PH), the subjects remained in
a semi-recumbent position in a climatic chamber. The method used
for the passive heating session has been described by Henane and
Valatx [17]. Briefly, the subjects were asked to lie down on a
balance (TESTUT 9009, Bethune, France; sensitivity = 3g) to measure
the sweat loss. A copper-constantan thermocouple was insulated and
inserted in the auditory canal. Climatic parameters were then
adjusted (successively Tdb = 45°C, rh = 70% and Tdb = 50°C, rh =
30%) to reach a rectal temperature = 38.5°C at 60 min, and
39°C at 120 min. After the period of hyperthermia, the
subjects stayed in a semi-recumbent position for a 60-min recovery
period under controlled thermal conditions (Tdb = 21-22°C, rh =
35-45%), until the last blood sample was taken.
During the three trials, a blood sample (10 mL) was taken
at 60, 120 and 180 min. The subjects then emptied their
bladder and were weighed. The subjects were not rehydrated during
any of the experiments.
Physiological measurements
During the E trial, the exercise intensity was checked by measuring
2 every 30 min over a 10-min period.
Plasma volume changes
Variations of PV changes (ΔVP) were calculated over time from
hematocrit and hemoglobin concentration variations according to the
Dill and Costill equation [18]. The hematocrit was multiplied by
the factor (0.96*0.91) to correct for trapped plasma and to convert
the venous hematocrit to a whole body hematocrit, and the
hemoglobin was multiplied by the factor 0.92 to convert the venous
hemoglobin to whole body hemoglobin according to Harrison et al.
[19]. The calculations of Dill and Costill equations used the
reference points adapted to the posture.
Hormonal analyses
After collection of blood into tubes containing lithium-heparin,
samples were centrifuged at 3000 g for 10 min. The supernatant
was removed and stored at –80°C until analysis. Plasma
catecholamines were measured using high performance liquid
chromatography with electrochemical detection. Plasma cortisol (ref
TKC01), and plasma prolactin (IRMA Count ref IKPR1) were assayed
using commercial kits (DPLC, La Garenne Colombes, France).
Leukocyte counts and hematocrit and hemoglobin
measurements
Blood (3 mL) was placed in EDTA tubes and analyzed for
differential white cell counts as routinely performed on PENTRA 120
Retic (ABX-France, Montpellier, France). This analysis included
hematocrit, hemoglobin measurements, determination of total white
blood cell numbers and neutrophil, monocyte, and lymphocyte numbers
in order to detect changes in circulating white blood cell
populations.
Whole blood assay
Venous blood was collected in heparinized tubes (15 IU/mL blood;
sodium heparin, ref 6541, Becton Dickinson, Rutherford, NJ, USA).
One hundred μL of whole blood aliquots were diluted with 400 μL of
RPMI 1640 (Sigma-Aldrich ref 50883, L’isle d’Abeau, Chesnes,
France), penicillin 100U.mL-1 and streptomycin 100
μg.mL-1 (Gibco ref 15140 and 15122), glutamine
4mM.mL-1 and mercaptoethanol 5x10-3
mol.mL-1. Diluted blood was stimulated either by LPS
1μg.mL-1 for 24h (E. coli, serotype, 055B11), either by
PHA 50 μg.mL-1 (Sigma-Aldrich ref L6143) for 48h. Twenty
four h and 48h corresponded to the maximum cytokines production.
Non-stimulated controls were examined under the same conditions.
During the incubation, the tubes were placed at 37°C + 5%
CO2. After the incubation, the tubes were spun for
10 min at 400 g, and the supernatants were collected and
stored at -80°C until assayed.
Cytokines were assayed in the supernatants with a Bio-Plex
system analyzer (Luminex X Map technology, Biorad, Marnes la
Coquette, France) and Human cytokine 2-plex for the detection of
IL-10, TNF-alpha (ref X50000005H, Biorad, Marnes la Coquette,
France) for the blood stimulated with LPS and Human cytokine 2-plex
for the detection of IL-10, INF-gamma (ref X50000001V, Biorad,
Marnes la Coquette, France) for the blood stimulated with PHA. The
minimum detectable concentrations were < 2
pg.mL-1.
Statistical analysis
Data analysis was performed with the Statistica® package
(Statsoft Inc, Tulsa, Oklahoma, USA). Statistical differences were
calculated with a two-way repeated-measures analysis of variance
design; when an overall difference was found, individual stages
were compared with the Tukey post hoc test. Data are presented as
mean ± SEM, and the null hypothesis was rejected when p < 0.05
for all analyses.
Results
Changes in rectal temperature (Tre)
In the PH and E trials, Tre increased gradually, reaching 38.5°C by
the end of the 60-min challenge, and 39°C by 120 min, while
the values remained steady around 37°C at the time of the test
control (p < 0.001 compared to C) (figure 1).
Plasma volume changes (ΔPV) and fluid losses
Plasma volume (table 1) did not change
significantly during the C and E trials, but showed an marked fall
during PH (p < 0.001 compared to C and E). Because of this
marked fall, all the values were corrected according to ΔPV. The
percentage of dehydration was 0.6 ± 0.1%, 3.5 ± 0.1% and 3.5 ± 0.1%
of body weight at the end of the C, PH and E tests,
respectively.
Table 1 Mean values (± SEM) of plasma volume
changes (ΔPV), leukocytes (103.mL-1),
neutrophils (103.mL-1), lymphocytes
(103.mL-1) and monocytes
(103.mL-1) changes corrected for ΔPV
|
|
0 min
|
60 min
|
120 min
|
end of recovery
|
|
ΔPV (%)
|
C
|
0
|
0.1 ± 0.6
|
-1.4 ± 1.0
|
-1.5 ± 1.2
|
|
HP
|
0
|
-12.3 ± 1.1 ccc-eee
|
-16.9 ± 1.7 ccc-eee
|
-13.3 ± 0.9 ccc-eee
|
|
E
|
0
|
-0.7 ± 1.1
|
-4.0 ± 1.4
|
-1.6 ± 1.1
|
|
Leukocytes
|
C
|
4.4 ± 0.4
|
4.7 ± 0.4
|
5.1 ± 0.5
|
5.1 ± 0.5
|
|
103. mL-1
|
HP
|
4.3 ± 0.3
|
4.6 ± 0.4
|
5.3 ± 0.9
|
5.7 ± 0.7
|
|
E
|
5.3 ± 0.7
|
8.1 ± 0.9 ccc-hhh
|
10.9 ± 1.1 ccc-hhh
|
10.0 ± 0.8 ccc-hhh
|
|
Neutrophils
|
C
|
2.3 ± 0.2
|
2.5 ± 0.2
|
2.9 ± 0.4
|
2.8 ± 0.4
|
|
103. mL-1
|
HP
|
2.2 ± 0.2
|
2.4 ± 0.2
|
3.3 ± 0.8
|
3.9 ± 0.6 □§
|
|
E
|
2.3 ± 0.2
|
4.4 ± 0.8 ccc-hhh
|
7.0 ± 1.1 ccc-hhh
|
8.0 ± 0.5 ccc-hhh
|
|
Lymphocytes
|
C
|
1.5 ± 0.2
|
1.6 ± 0.1
|
1.6 ± 0.1
|
1.7 ± 0.1
|
|
103. mL-1
|
HP
|
1.5 ± 0.1
|
1.6 ± 0.2
|
1.5 ± 0.1
|
1.3 ± 0.1
|
|
E
|
1.8 ± 0.2
|
2.4 ± 0.2 ccc-hhh
|
3.0 ± 0.3 ccc-hhh
|
1.7 ± 0.1
|
|
Monocytes
|
C
|
0.36 ± 0.03
|
0.39 ± 0.04
|
0.40 ± 0.04
|
0.35 ± 0.03
|
|
103. mL-1
|
HP
|
0.37 ± 0.03
|
0.36 ± 0.04
|
0.32 ± 0.05
|
0.33 ± 0.04
|
|
E
|
0.39 ± 0.04
|
0.63 ± 0.06 ccc-hhh
|
0.83 ± 0.08 ccc-hhh
|
0.58 ± 0.05 ccc-hhh
|
Plasma epinephrine and norepinephrine
Plasma catecholamines did not change significantly during the C and
PH trials (figure 2). However,
they rose markedly during the exercise (p < 0.001 compared to C
and PH, p < 0.01 compared to time 0). The plasma rates returned
to the reference values by the end of recovery (p < 0.01
compared to time 120 min). During the exercise, plasma
epinephrine was at 3332 ± 517 nmoL.L-1, 3932 ± 608
nmoL.L-1 and 1447 ± 213 nmoL.L-1, and plasma
norepinephrine at 5843 ± 944 nmoL.L-1, 11176 ± 1629
nmoL.L-1 and 2981 ± 554 nmoL.L-1 at time
60-min 120-min and 1-h recovery, respectively.
Plasma cortisol and prolactin
The circulating cortisol rates showed a progressive and significant
fall during the C test, in relation to the circadian rhythm (p <
0.05 compared to time 0) (figure 3). The levels
increased at 120 min during the E and PH tests (16 ± 1
μg.dL-1, 15 ± 1 μg.dL-1 respectively, p <
0.05 compared to the C trial). Plasma cortisol then continued to
increase after the exercise (19 ± 2 μg.dL-1, p <
0.001 compared to C and PH, p < 0.01 compared to time
120 min), while it returned to the basal values during the
recovery of PH (12 ± 1 μg.dL-1, p < 0.01 compared to
time 120 min). Plasma prolactin did not change significantly
during the C trial. The concentrations increased slightly but
nonsignificantly during the exercise when Tre was at 39°C. It
showed a large increase at time 60 and 120 min during PH (19 ±
4 mg.mL-1 and 21 ± 2 mg.mL-1 respectively, p
< 0.001 compared to C and E, p < 0.01 compared to time
0 min), and returned to basal values by the end of the
recovery (9 ± 1 mg.mL-1, p < 0.01 compared to time
120 min).
Total leukocytes and subsets changes
The exercise induced a significant mobilization of circulating
leukocytes, neutrophils, lymphocytes and monocytes (p < 0.001
compared to C and PH) (table 1). The
number of leukocytes, and subsets showed a 100% increase. A peak of
neutrophils appeared at the end of the recovery during the PH
(+39%) and E trials (+180%) (p < 0.05 compared to time
120 min). The monocytes remained high at the end of the
recovery (+65%, compared to C and PH, p < 0.05). Except that,
the concentrations of the leukocytes, lymphocytes and monocytes did
not change during C and PH.
LPS-induced TNF-α and IL-10 production
The controls produced negligible quantities of cytokines in the
supernatants (figure 4). As the
absolute values were very different from one individual to another,
the results of cytokines assays on cell culture supernatant are
presented as relative changes. The response to LPS increased
slightly, but not significantly during the C trial. We observed a
reduction in TNF-α at the end of the PH and E trials when Tre =
39°C (ΔTNF-α = -16 ± 6% and -21 ± 8% for the PH and E trials,
respectively, p < 0.001 compared to C). This reduction was
clearly amplified at the end of recovery (ΔTNF-α = -32 ± 3% and -38
± 6% for the PH and E trials, respectively, p < 0.001 compared
to C, p < 0.001 compared to Time 60 min). The production of
TNF-α during PH and E was similar in spite of a different number of
monocytes. In addition, only the exercise stimulated IL-10
production after stimulation of blood with LPS (ΔIL-10: = +59 ± 10%
and +79 ± 19 at time points 60 and 120 min respectively, p
< 0.001 compared to C and PH, p < 0.001 compared to time
0 min).
PHA-induced INF-γ and IL-10 production
The controls produced negligible quantities of cytokines in the
supernatants. E and PH induced a decrease in the production of
INF-γ, as shown in figure 5, at the end
of the 39°C challenge until the end of recovery. At 39°C, ΔINF-γ =
-23 ± 5% and -23 ± 11% for the PH and E trials, respectively (p
< 0.001 compared to C, p < 0.001 compared to time point
60 min). The production of INF-γ during the PH and E trails
was similar in spite of a different number of monocytes. At 1-h
recovery, ΔINF-γ = -38 ± 7% and -66 ± 8% for the PH and E trials,
respectively (p < 0.001 compared to C, p < 0.001 compared to
time point 60 min). At this time, the difference between PH
and E was not significant. We did not observe a significant effect
of E and PH on the production of IL-10.
Discussion
The Tre time courses were similar during E and PH. However, the
stress hormones responses were different according to the nature of
the challenge. The plasma levels of catecholamines were increased
only during E, prolactin was increased only during PH, whereas
cortisol was increased during both E and PH. In the same period,
the main results of the immune responses showed that only the
exercise caused a marked mobilization of blood leukocytes and
leukocyte subsets. The TNF-α and INF-γ production by stimulated
blood was inhibited in an substantial way in both E and PH compared
to the control when Tre reached 39°C. IL-10 production was enhanced
only during exercise when blood was stimulated with LPS. Both
challenges raised Tre, to 39°C compared to 38.5°C, and were still
effective 1 h after the end of the challenges.
As has been previously shown [20], the present results confirm
that, for the same level of dehydration, plasma volume is better
preserved during exercise than during passive heat exposure. The
marked fall in PV during PH justifies the correction of hormonal
values according to ΔPV.
Hormonal changes
The differences that we observed in the hormonal responses are in
good agreement with the current state of knowledge. Exercise
increases catecholamines, but passive hyperthermia does not. The
lack of increase in plasma catecholamines during passive
hyperthermia versus exercise has already been described [2, 3],
with a rise in core temperature of 0.7°C for Brenner et al. 1997
[2], and 2°C, for Melin et al. [3], as in our study.
During prolonged, submaximal exercise, increases in cortisol
levels coincide with a decrease in blood glucose concentration [1].
It is probably for this reason that it increased from the
60th min of exercise in our study, but not in the study
of Brenner et al. [2], where the exercise was shorter and less
intense. The increase in cortisol concentrations during passive
heating seems however, to have had more attention. For Møller et
al. [13], a 3-h warm bath induced a peak of circulating cortisol,
while for Brenner et al. [2] two bouts of 30-min in a climatic
chamber at 40°C, 30% relative humidity did not alter the
concentrations of this hormone. In our study, the increase in
plasma cortisol appeared between 60 and 120-min of passive heating.
Won and Lin [21] have shown in mice that passive thermal stress
produced marked accumulation of adrenal cortisol. One can suppose
that the exposure time to heat and the level of relative humidity
(which intensifies the challenge with heat) are factors that can
explain the differences between our results and Brenner’s. Plasma
cortisol returned to basal levels during PH recovery, because the
heat challenge had disappeared. However, during recovery from the
exercise, plasma cortisol was significantly increased compared to
the levels observed at the end of the exercise. Utter et al. [22]
have shown that lack of carbohydrate substrate availability could
induce higher levels of cortisol. In our study, the long duration
of the exercise and the lack of water and carbohydrate supply could
explain the cortisol peak at 1-h of recovery.
Plasma prolactin concentrations increased slightly, but
nonsignificantly during exercise when Tre was at 39°C, but showed a
clear increase during PH. Our results are in agreement with the
current state of knowledge [4]. Circulating plasma prolactin
concentrations increases during exercise are largely in response to
the ambient temperature, with lower rises for a thermoneutral
ambient temperature [23]. However, an increase in body temperature
at rest induced by external heating is a stimulus for prolactin
secretion [4]. Thus, these different hormonal responses may have a
role in the differences in immune responses observed during E and
PH.
Immune responses
Only exercise induced a significant mobilization of circulating
leukocytes and leukocyte subsets. It is now well known that
catecholamines are responsible for this effect [24]. This is why
Kappel et al. [14] observed leukocytosis during passive
hyperthermia by immersion in warm water; they also saw an increase
in plasma catecholamines. In our study, there were no plasma
catecholamine changes and no leukocytosis during PH. However, these
changes in immunocompetent cells can also depend on the Tre. Dubose
et al. [25] have observed leucocytosis in subjects presenting
exertional heat injury, with Tre > 40°C. During the recovery,
the neutrophils were increased in both E and PH trials. This could
be an effect of cortisol according to Rhind et al. [12], and also
of granulocyte colony stimulating factor (G-CSF), according to
Ellis et al. [26].
E and PH induced a marked decrease (40%) in the production of
TNF-α by immune blood cells stimulated with LPS from the end of the
39°C challenge to 1-h recovery, while there was no change during
the C trial. However, if these results are compared against the
monocyte count changes, the TNF-α production by monocytes is higher
during PH than during E. To our knowledge, there are very few
studies on this subject. Starkie et al. [27, 28] found by flow
cytometry, that there was a decrease in the amount of TNF-α per
cell post-compared with pre-exercise, which is in good agreement
with our results. For Kappel et al. [8], hyperthermia after
immersion did not influence the production of cytokines from
stimulated blood cells. In vitro, when cells are stimulated with
LPS and submitted to a pre-stress with a mild heat shock, cytokine
production is decreased compared with controls [7, 9, 29, 30].
Cortisol plays an important role in the inhibition of TNF-α
secretion [11, 16]. The higher TNF-α production by monocytes with
PH could be an effect of prolactin [10]. Catecholamines may be
implicated in the low production of TNF-α by monocytes, since, in
the blood of healthy volunteers, epinephrine reduced the TNF-α mRNA
concentration after stimulation by LPS, as reported by Bergmann
[31]. They play a part, nevertheless in the monocyte count
increase.
Exercise strongly enhanced LPS-stimulated IL-10 production
(+70%), while there was no variation in the IL-10 production during
PH. This increase could be due to the increase in the number of
monocytes induced by catecholamines [24]. Moreover, they enhance
the production of IL-10 in human whole blood cultures stimulated
with LPS [31]. These effects are mediated by stimulation of
β-adrenoceptors [32]. In the blood of healthy volunteers,
epinephrine increased the LPS-stimulated IL-10 blood production by
77.8%. The absence of an increase in the plasma catecholamines and
so, the absence of change in the monocyte count, explains the
absence of IL-10 production during PH.
E and PH induced a marked decrease (60%) in the production of
INF-γ by immune blood cells stimulated with PHA from the end of the
39°C challenge to 1-h recovery, while there was no change during
the C trial. If these results are set against the lymphocyte count
changes, the INF-γ production by lymphocyte is higher during PH
than during E. It is acknowledged that PHA-stimulated cell
responses decrease during exercise, as estimated by flow cytometry
[33-35] and fluorescence intensity methods [25]. Mitchell et al.
[35] observed, as we did, a greater decrease during the recovery
period, with complete restoration 24 h after the end of the
exercise. To our knowledge, there are few data dealing with the
effect of passive hyperthermia on the response to mitogens.
According to Dubose et al. [25], T lymphocyte subsets showed
reduced PHA responses both in exertional heat injury subjects and
exercised subjects. However, the reduction was significantly
greater in heat injury subjects compared to exercise subjects
without heat illness. In this study, the Tre of exertional heat
injury subjects was above 40°C. Another experiment using immersion
in warm water [6], showed that the stimulation of lymphocytes of
hyperthermic men which would have an inductive role on the
secretion of INF-γ, produces as much as 10-fold more INF-γ than
cells taken at basal temperatures from the same individuals. In our
study, both exercise and passive hyperthermia suppress the
production of INF-γ, probably by a direct effect of cortisol [11,
16]. The higher TNF-α production by monocytes with PH could be an
effect of prolactin, which would have an inductive role on the
secretion of INF-γ [10]. At 1-h recovery, the suppression of the
production of TNF-α was less for the PH trial. This could be
explained by the lower cortisol levels and also by an effect of
prolactin. We did not observe any significant effect on IL-10.
Conclusion
We screened only a part of the immune response. After stimulation
of monocytes and T-lymphocytes, cortisol and catecholamines inhibit
the production of pro-inflammatory cytokines, while prolactin
stimulates it. So prolactin and catecholamines have conflicting
roles and this might explain the less marked inhibition of
pro-inflammatory cytokines during PH compared to E, whereas
cortisol exerts similar effects during both trials. These effects
became major when Tre reached 39°C. Consequently, exercise and
passive hyperthermia, via the stress hormones, promote Th2
responses, since they decrease the production of pro-inflammatory
cytokines and enhance the production of anti-inflammatory cytokines
[16]. It could induce immunosuppression or a protection of the
organism from systemic “overshooting” with Th1/pro-inflammatory
cytokines, as suggested by Elenkov [16] and Petersen [36]. However,
these authors propose this beneficial effect only during exercise.
In our study, this effect also applied to passive hyperthermia.
Nevertheless, the trend towards protection against inflammation is
stronger for exercise than for passive hyperthermia, because of the
hormones involved.
Acknowledgements
The authors thank D. Guicherd for the catecholamines assay. The
excellent technical assistance of A. Roux, J. Denis, L.
Vachez-Collomb and N. Clerc is also gratefully acknowledged. The
authors extend their thanks to the volunteers whose participation
made this study possible.
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