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Effects of whole-body cryotherapy on serum mediators of inflammation and serum muscle enzymes in athletes

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Effects of whole-body cryotherapy on serum mediators of inflammation and serum muscle enzymes in athletes

Abstract

Whole-body cryotherapy (WBC) covers a wide range of therapeutic applications and consists of briefly exposing the body to extremely cold air. In sports medicine, WBC is used to improve recovery from muscle injury; however, empirical studies on its application to this area are lacking. To fill this gap, we compared changes in immunological parameters (C3, IgA, IgM, IgG, C-reactive protein, PGE2), cytokines (IL-2, IL-8, IL-10), adhesion molecules (sICAM-1), and muscle enzymes (creatine kinase [CK], lactate dehydrogenase [LAD]) before and after WBC in 10 top-level Italian National team rugby players. The subjects underwent five sessions on alternate days once daily for 1 week. During the study period, the training workload was the same as that of the previous weeks. Compared to baseline values, immunological parameters remained unchanged, while CK and LAD levels significantly decreased after treatment. No alterations in immunological function were observed but there is a decrease in pro-inflammatory cytokine/chemokine and an increase in anti-inflammatory cytokine.As measured by changes in serum CK and LAD concentrations, and cytokines pathway, short-term cold air exposure was found to improve recovery from exercise-induced muscle injury and/or damage associated with intense physical training.
Effects of whole-body cryotherapy on serum mediators of inflammation
and serum muscle enzymes in athletes
Giuseppe Banfi
a,b
, Gianluca Melegati
a,c
, Alessandra Barassi
d
, Giada Dogliotti
e
,
Gianvico Melzi d’Eril
d
, Benoit Dugue
´
f
, Massimiliano M. Corsi
a,e,
a
Istituto Ortopedico R. Galeazzi, IRCCS, 20161 Milan, Italy
b
Department of Health Technology, University of Milan, Milan, Italy
c
Italian Rugby Federation, Italy
d
Department of Medicine and Surgery, San Paolo Hospital, University of Milan, Milan, Italy
e
Laboratory of Clinical Pathology, Institute of General Pathology, Medical Faculty, University of Milan, 20133 Milan, Italy
f
Laboratoire des Adaptations Physiologiques aux Activite
´s Physiques, Universite
´de Poitiers, 86034 Poitiers Cedex, France
article info
Article history:
Received 13 May 2008
Accepted 31 October 2008
Keyword:
Inflammation
Cryotherapy
Athletes
abstract
Whole-body cryotherapy (WBC) covers a wide range of therapeutic applications and consists of briefly
exposing the body to extremely cold air. In sports medicine, WBC is used to improve recovery from
muscle injury; however, empirical studies on its application to this area are lacking. To fill this gap, we
compared changes in immunological parameters (C3, IgA, IgM, IgG, C-reactive protein, PGE2), cytokines
(IL-2, IL-8, IL-10), adhesion molecules (sICAM-1), and muscle enzymes (creatine kinase [CK], lactate
dehydrogenase [LAD]) before and after WBC in 10 top-level Italian National team rugby players. The
subjects underwent five sessions on alternate days once daily for 1 week. During the study period, the
training workload was the same as that of the previous weeks. Compared to baseline values,
immunological parameters remained unchanged, while CK and LAD levels significantly decreased after
treatment. No alterations in immunological function were observed but there is a decrease in pro-
inflammatory cytokine/chemokine and an increase in anti-inflammatory cytokine.
As measured by changes in serum CK and LAD concentrations, and cytokines pathway, short-term
cold air exposure was found to improve recovery from exercise-induced muscle injury and/or damage
associated with intense physical training.
&2008 Elsevier Ltd. All rights reserved.
1. Introduction
Whole-body cryotherapy (WBC) consists of brief exposure to
extreme cold in a temperature-controlled chamber (110 1C)
(Westerlund et al., 2004). It is applied to relieve pain and
inflammatory symptoms caused by numerous disorders, particu-
larly those associated with rheumatic conditions, and is recom-
mended for the treatment of arthritis, fibromyalgia and
ankylosing spondylitis. In sports medicine, WBC has gained wider
acceptance as a method to improve recovery from muscle injury;
however, no controlled studies have been published so far.
WBC has been shown not to be deleterious to lung function
(Smolander et al., 2006) or to decrease antioxidant capacity
(Dugue
´et al., 2005) or propiomelanocortin-related hormones
(Fricke et al., 1988). In a previous study, we demonstrated that
WBC does not enhance hematological values, as measured by
hemoglobin concentration and counts of erythrocytes, reticulo-
cytes, leukocytes, and platelets in peripheral blood (Banfi et al.,
2008). Studies investigating the effects of cold exposure on
immune function (Walsh and Whitham, 2006) found that
lymphocyte, monocyte and tumor necrosis factor
a
levels were
increased, whilst concentrations of interleukins IL-6, IL-1
b
, and
C-reactive protein (CRP) were unchanged after 6 weeks of cold
water immersions (Jansky et al., 1996). Moreover, resting levels of
IL-6, lymphocytes and monocytes were noted to be higher in
subjects accustomed to winter swimming than in inexperienced
individuals (Dugue
´and Leppa
¨nen, 2000). Contrary to popular
belief, cold exposure can actually stimulate rather than depress
immune function (Walsh and Whitham, 2006) In general, WBC
does not appear to be harmful; indeed, it may be beneficial for
athletes since prompt recovery from muscle injury is a primary
concern for both athletes and sports physicians alike. Despite the
wealth of literature on rehabilitation techniques, published data
on WBC in rehabilitation programs are scarce. Studying the effects
of WBC can have practical value not only for many physiological
ARTICLE IN PRESS
Contents lists available at ScienceDirect
journal homepage: www.elsevier.com/locate/jtherbio
Journal of Thermal Biology
0306-4565/$ - see front matter &2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.jtherbio.2008.10.003
Corresponding author at: Istituto Ortopedico R. Galeazzi, IRCCS, 20161 Milan,
Italy.
E-mail address: mmcorsi@unimi.it (M.M. Corsi).
Journal of Thermal Biology 34 (2009) 55–59
and clinical purposes, but also for determining clinical signifi-
cance in the context of antidoping testing, since techniques that
accelerate recovery may be classified as prohibited. Furthermore,
post-WBC treatment changes in biochemical and hematological
parameters could result outside the threshold range imposed by
sports federations and official control agencies, with the athletes
classified as being doped, or could be interpreted as an attempt to
mask changes caused by illicit treatment different from WBC.
The aim of this study was to determine whether WBC had a
positive effect on musculoskeletal metabolism, recovery from
exertional muscle damage, and immune function. Biochemical
and immunological markers were measured at baseline and after
1 week of WBC treatment (five once-daily sessions) in 10 male
rugby players selected randomly from the Italian National team.
2. Methods
Ten male athletes (mean age 2672.5 years; mean body-mass
index 27.572.3 kg/m
2
) underwent once daily WBC treatment for
5 days (Monday–Wednesday, Friday, and Saturday) at the Olympic
Rehabilitation Center of Spa"a (Poland). Wearing minimal cloth-
ing, the subjects were first exposed to very cold air (30s at 60 1C)
then to extremely cold air (2 min at 110 1C). They reported an
improved sense of general well-being and no discomfort or
disturbance.
During the study period, the subjects continued with their
regular training. The workload was the same as in the previous
6 weeks. Training consisted of 3 h of daily exercises: 1 h of
maximal training in the morning, followed by 1h of submaximal
effort, then 1 h of submaximal training in the afternoon, in
addition to conditioning exercises.
No illnesses occurred during the study period. Diet was
controlled and identical to that of the previous 6 weeks.
The 10 subjects were chosen randomly from the Italian
National rugby team (30 athletes). All gave informed consent to
the study protocol. Blood samples were drawn by vacutainer
tubes at 8 a.m. on the first day of treatment (Monday) and then at
the end of treatment on the following Monday. All subjects
continued with the same training workload as that of the previous
weeks. The time period from the last intense training session was
the same for both blood drawings. The serum samples were
separated within 3 h from drawing and stored at –20 1C until
assayed. All biochemical parameters were measured on a Roche
Modular (Roche, Basel, Switzerland), except for high-sensitivity
CRP (hs-CRP), which was measured nefelometrically on a BN
ProSpec analyzer (Behring, Marburg, Germany). PGE2, cytokines
(IL-2, IL-8, IL-10) and sICAM-1 were measured with ELISA kits
(R&D Systems, Minneapolis, MN, USA) and read on an spectro-
photometer (GDV, Milan, Italy).
Statistical analysis was performed using the paired ttest on a
MedCalc program (Mariawerke, Belgium). Statistical significance
was set at po0.05.
3. Results
Table 1 compares pre- and post-treatment blood chemistry
values. A slight but not significant increase in Ig and a slight but
not significant decrease in CRP were noted. Lymphocyte and
monocyte counts remained substantially unchanged (p¼n.s.):
44.778.2% versus 37.8710.6% and 9.671.7% versus 9.673.5%,
respectively. LAD and CK both decreased significantly:
307.77103.2U/L versus 183.9783.4 U/L and 362.3734.3 U/L
versus 318.4728.6 U/L, respectively. The standard deviation in
the post-treatment values decreased, indicating a greater uni-
formity of data.
The hs-CRP assay is a highly sensitive test for in measuring CRP
levels in inflammation associated with rheumatoid arthritis and
cardiac disease. The results of the hs-CRP test were similar to
those obtained with conventional CRP testing. The mean hs-CRP
before and after WBC was 0.8870.40 and 0.7770.40 mg/L,
respectively (p¼n.s.). Table 2 shows pro-inflammatory cytokines,
prostacyclin, and adhesion molecule: a slight significant decrease
of IL-2 (po0.05) and IL-8 (po0.05), and a very significant increase
of IL-10 (po0.05) were noted. PGE2 was significantly decreased
(p¼o0.0001). Moreover also sICAM-1 decreased in a very
significant way (po0.01) (Fig. 1)
4. Discussion
The use of methods other than passive recovery for improving
recovery after intense training and competitions in sports is
growing. In particular, in rugby, the use of cold water, possibly
associated with active recovery (cycling), and the use of cold and
hot water immersion are quite popular. WBC refers to brief
exposure to very cold air for treating symptoms of various
illnesses. In sports medicine, WBC is administered to improve
recovery from muscular trauma. As specific studies are lacking, we
measured immunological and muscular markers in 10 top-level
rugby players of the Italian National team before and after a
1-week course of daily sessions of WBC. The cold has also been
shown to increased concentrations of anti-inflammatory cyto-
kines in peripheral blood: it is suggested to have local and
systemic anti-inflammatory effect.
We chose to compare changes in immunoglobulin and CRP
levels because they are reliable indicators of acute or chronic
infection and/or inflammation. Widely available in clinical
laboratories, these markers are routinely and easily evaluated in
the general population and in athletes. Lymphocyte and monocyte
counts and plasma IL-6 concentrations are known to be higher in
experienced than in inexperienced winter swimmers, probably
ARTICLE IN PRESS
Table 1
Serum concentration of immunological markers and muscle enzymes before and
after whole-body cryotherapy (WBC) in 10 top-level rugby players.
Before WBC After WBC Pvalue
IgG (mg/dL) 1262.47196.5 1286.37186.4 n.s.
IgM (mg/dL) 97.9733.7 100.5735.1 n.s.
IgA (mg/dL) 240.17106.2 250.37116.3 n.s.
CRP (mg/dL) 0.7470.43 0.6270.38 n.s.
C3 (U/L) 140.3720.9 142.5721.6 n.s.
CK (U/L) 307.77103.2 183.9783.4 o0.01
LAD (U/L) 362.3734.3 318.4728.6 o0.01
PGE2 (pg/mL) 1162.97292.3 351.57179.9 o0.0001
7values are means7SD. CRPC-reactive protein; C3C3 proactivator; CK
creatine kinase; LADlactate dehydrogenase; PGE2prostaglandin E2.
Table 2
Serum concentration of cytokines and adhesion molecule before and after whole-
body cryotherapy (WBC) in 10 top-level rugby players.
Before WBC After WBC Pvalue
IL-2 pg/mL 11.3775.91 6.4773.66 o0.05
IL-8 pg/mL 10.3072.31 8.1872.11 o0.05
IL-10pg/mL 41.1573.07 45.8473.55 o0.01
SICAM-1 ng/mL 196.147113.12 74.68744.11 o0.01
IL-2interleukin-2; IL-8interleukin-8; IL-10interleukin-10; sICAM-1soluble
intercellular adhesion molecule 1.
G. Banfi et al. / Journal of Thermal Biology 34 (2009) 55–5956
because of long duration exercise in a cold environment by
experienced subjects. WBC is not characterized by changes in
immunological markers and does not seem to impair immune
function, as measured by using immunological parameters with
paracrine activity (Dugue
´and Leppa
¨nen, 2000). It is not clear how
WBC relieves pain and other symptoms of rheumatoid arthritis
and arthropathies in general, but local cryotherapy has been
shown to exert an analgesic effect on and a protective effect
against collagenase on cartilage (Harris and McCroskery, 1974).
The effect of WBC may be linked to alterations of paracrine
molecules rather than to systemic immune functions. In sports
medicine, WBC has gained wider acceptance as a procedure to
improve recovery from muscular trauma; however, controlled
studies on athletes are lacking.
ARTICLE IN PRESS
PGE 2
Before WBC After WBC
0
500
1000
1500
Before WBC
After WBC
pg/mL
Before WBC After WBC
0
100
200
300
Before WBC
After WBC
ng/mL
Before WBC After WBC
0
10
20
30
40
50
Before WBC
After WBC
pg/mL
Before WBC After WBC
0
5
10
15
Before WBC
After WBC
pg/mL
IL-10
sICAM-1 IL-8
IL-2
Before WBC After WBC
0
5
10
15
Before WBC
After WBC
pg/mL
CK
Before WBC After WBC
0
100
200
300
400
Before WBC
After WBC
U/L
LAD
Before WBC After WBC
0
100
200
300
400 Before WBC
After WBC
U/L
Fig. 1.
G. Banfi et al. / Journal of Thermal Biology 34 (2009) 55–59 57
Published data suggest that WBC has no detrimental effect on
immunological parameters, although the observation period in
this study was too short to evaluate changes in lymphocyte
involvement and function. Long-term cold water immersion
of healthy males is known to produce slight increases in
plasma TNF
a
, lymphocytes and monocytes (Jansky et al., 1996)
Specific studies on immunoglobulins during and after WBC are
lacking, however.
Several studies have investigated the effect of cold stress on
immune system function. Cold exposure in a climate chamber at
51C induced a small, but significant leukocytosis due to an
increase in circulating neutrophils and lymphocytes, accompanied
by natural killer cell activity (Brenner et al., 1999). The authors
remarked that cold exposure had an immunostimulating effect
that was possibly related to an enhanced noradrenaline response
to the cold.
There is, in general, limited evidence indicating that short- or
long-term cold exposure causes immunosuppression. In contrast,
a stimulating effect of cold exposure was found to depend on the
relationship between the decrease in core temperature and the
duration of cold exposure (Walsh and Whitham, 2006) In one
study, IgA and IgM concentrations were reported to be lower
during the first 4 months of a 1-year Antarctic expedition
(Gleeson et al., 2000). The change in mucosal immunity was
related to the psychological stress of the expedition, but no
increase in upper respiratory tract infections was observed. It
could be argued that long-term cold exposure, especially when
associated with psychological discomfort and mood modifica-
tions, depresses immunoglobulin production and release, whereas
very short cold exposure does not affect Ig levels. Moreover, cold
inhibits the expression of inflammatory mediators; hypothermia
inhibits activation of neutrophils and expression of intercellular
adhesion molecule-1 (ICAM-1), the adhesion and activation of
neutrophils during inflammation (Hanusch et al., 2007). Therefore
hypothermia induced expression of the anti-inflammatory cyto-
kines IL-10 (Scumpia et al., 2004); hypothermia attenuates the
inflammatory response during WBC, thus contributing to its
beneficial role in organ protection (Hofstetter et al., 2007). As
elevated serum CK is a characteristic marker of exertional
rhabdomyolysis, it may be used for measuring the effects of
workload, recovery and possible overtraining. In a previous study
on top-level rugby players, we found that active recovery with leg
immersion in cold water after training produced beneficial effects
and a decrease in serum total CK concentration in comparison
with passive recovery (Banfi et al., 2007). These results were in
line with those of Gill et al. (2006) observed in rugby players by
measuring CK in interstitial muscular fluid. It seems that acute
exposure of the whole body to cold air stimulates muscle fiber
repair by reducing cell membrane breakdown or increased cell
permeability caused by oxidant agents produced during physical
exercise (Banfi et al., 2006). In our subjects, the significant
decrease in serum total CK concentration suggested rapid
recovery from muscle damage, since the athletes did not change
the training scheme or workload during the study period.
No published data are available about the behavior of CK and
LAD after WBC. The mechanism underlying the decrease in
muscle enzyme levels is unknown. The normal response of the
human body to cold exposure is accelerated elimination of
triiodothyronine (T3) and activation of the sympathetic nerve
system, which increases the release of noradrenaline in the blood
(Leppa
¨luoto et al., 2005). The augmented T3 catabolism is not
accompanied by activation of the pituitary–thyroid axis during
long-term cold exposure, but rather by a hypothyroid-like status
(Leppa
¨luoto et al., 2005). Concentrations of thyroid-stimulating
hormone, tetraiodothyronine and T3 were unchanged in WBC-
treated patients with rheumatoid arthritis (Zagrobelny et al.,
1992). However, even if short-term cold exposure could influence
thyroid metabolism, CK is elevated in subclinical hypothyroidism
(Hekimsoy and Oktem, 2005). Thyroid response to cold exposure
could perhaps act through a decreased sensitivity of mitochondria
to ADP and creatine, as well as mitochondrial CK, influencing the
entire CK (and muscle isoenzyme LAD) metabolism (Athe
´a et al.,
2007). Sustained noradrenaline stimulation during long-term cold
exposure and WBC could play a role in relieving pain and creating
an enhanced sense of well-being. However, in top-level athletes
exercising in a cold environment, there is a simultaneous increase
in noradrenaline and CK levels, with the noradrenaline increase
generally higher than that of CK (seven-fold versus two-fold),
when compared with baseline values (Rønsen et al., 2004)
Noradrenaline stimulation cannot completely explain the CK
decrease in our subjects after WBC treatment, but it may have
triggered a cascade of events that induced the decrease.
WBC had no adverse effect on the immunological status of the
subjects and had a positive effect on CK and LAD levels.
Moreover, there is an increase of anti-inflammatory cytokine
IL-10, and a decrese of pro-inflammatory cytokine IL-2 and
chemokine IL-8. We confirmed the decrease of sICAM-1 induced
by cold treatment, inducing an anti-inflammatory response, also
correlated to decrease of PGE2. PGE2 is synthesized in substantial
amounts at sites of inflammation where it acts as a potent
vasodilator and sinergistically with other mediators such as
histamine and bradykinin causes an increase in vascular perme-
ability and edema. Moreover, PGE2 is a central mediator of febrile
response triggered by the inflammatory process and intradermal
PGE2 is hyperalgesic in the peripheral nervous system.
The blood chemistry values demonstrate that this treatment
cannot be considered as an illegal or unethical procedure, e.g.,
blood boosting (Banfi et al., 2008). Additional studies on
physically active subjects are needed to confirm these findings,
possibly including case-control protocol.
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ARTICLE IN PRESS
G. Banfi et al. / Journal of Thermal Biology 34 (2009) 55–59 59
... In patients with inflammatory rheumatic diseases (Lange et al., 2008) and in professional tennis players (Ziemann et al., 2012) the decrease in TNFα concentrations was comparable to that previously reported after low-intensity exercise (Petersen and Pedersen, 2005). Banfi et al. assessed the effect of WBC on serum mediators of inflammation in athletes who reported increased concentrations of anti-inflammatory cytokines and a decrease in the pro-inflammatory cytokines/chemokines, IL-2, and IL-8 (Banfi et al., 2009b) in peripheral blood as a consequence of local and systemic analgesic effects of WBC. IL-6 can act both as a pro-inflammatory cytokine and as an anti-inflammatory myokine depending on its production site, the stimulation pathway that enabled its release, and its basal concentration (Villar-Fincheira et al., 2021). ...
... Nevertheless, in two different studies on men with obesity, 10 sessions of WBC did not significantly alter IL-6 concentrations (Dulian et al., 2015;Ziemann et al., 2013a), while its decrease after 10 sessions was reported only in LCF subjects with obesity and not in the HCF group with obesity (Ziemann et al., 2013a). It has already been shown that IL-10, an anti-inflammatory cytokine with multiple, pleiotropic effects in immunoregulation and inflammation, increases in rugby players after 5 sessions of WBC (Banfi et al., 2009b). In HCF and LCF subjects with obesity, 10 sessions of WBC increased IL-10 and the rise was sustained 24 h after the last session. ...
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Currently, all available therapies for the control and management of fibromyalgia (FM) are mostly focused on relieving patients’ symptoms and improving their quality of life. The purpose of this review is to provide an up-to-date overview of the evidence supporting the beneficial effects of whole-body cryostimulation (WBC) in patients with FM and evidence-based guidance on the possible adjuvant use of WBC in the treatment of FM. We searched the most recent literature by retrieving 10 eligible studies, 4 of which were abstracts only, from a total of 263 records. Thermal stress caused by cryostimulation induces an analgesic effect, improving pain, redox balance, and inflammatory symptoms in an exercise-mimicking fashion. In addition, it reduces the feeling of fatigue, improves mood, and reduces mental health deterioration with positive consequences on depressive states and improved sleep quality. Although the studies included in this review are not of sufficient quality and quantity to draw definitive conclusions about the effectiveness of WBC in FM, initial evidence indicates WBC as a promising add-on option in the multidisciplinary treatment of FM, due to its rapid action and high patients’ compliance. The application of WBC protocols has the potential to expand therapeutic options for the treatment of FM and related disorders; however, larger, high-quality primary studies are still needed.
... Specifically, we asked: 1) will 20-min of unilateral ankle or knee joint cooling applied to the dominant-leg change a flight time following two-legged maximal countermovement vertical jump? and 2) will the unilateral ankle or knee joint cooling alter jumping or landing kinematics and kinetics in the lower-extremity? As the temperature of the ankle or knee joint decreases due to joint cooling, subjects would experience several changes, such as afferent sensory information [13], nerve conduction velocity [20], enzyme process [21], and synovial fluid [22]. As a result, lower-extremity muscle contraction speed [23] during the jumping and landing tasks would be altered. ...
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OBJECTIVES This study examined the immediate effect of unilateral ankle or knee joint cooling on the low-erextremity kinematics and kinetics during two-legged jumping and landing.METHODS Twenty healthy adults randomly completed three data collection sessions for ankle or knee joint cooling, or control. For each session, participants performed two-legged countermovement jumps and lands. For joint cooling, two ice bags were directly placed to the right side and secured with a compression bandage. A three-dimensional motion analysis system (200 Hz) with two floor-embedded force platforms (2000 Hz) was employed to capture the jumping and landing. The cooling effects on kinematical (flight time, and sagittal plane joint angles) and kinetical (peak vertical ground reaction force (vGRF), impulse, and sagittal plane joint moments) variables were examined. A mixed-model analysis of variance was performed for each dependent variable ( p ≤0.0001 for all tests).RESULTS We did not observe any interactions (flight time: F<sub>2,95</sub>=0.67, p =0.52; joint angles: F<sub>2,209</sub>≤2.26, p ≥0.10; peak vGRF: F<sub>2,209</sub>≤1.76, p ≥0.20; impulse: F<sub>2,209</sub>≤2.54, p ≥0.10; joint moments: F<sub>2,209</sub>≤4.80, p ≥0.01 for all interactions). Regardless of condition and time (side effect), subjects showed a dominant-leg predominant movement strategy. Specifically, the right side showed a greater peak vGRF (2%), and greater ankle (7%), knee (6%), and hip (11%) joint moments, as compared with the left side during jumping. The same movement pattern was observed during landing that there was greater peak vGRF (11%) and impulse (8%), and greater ankle and knee joint moments (15%). Regardless of time and side (condition effect), subjects with ankle joint cooling showed 5% lesser ankle joint moment during jumping, compared with those who received knee joint cooling ( p =0.0001).CONCLUSIONS A 20-min of unilateral ankle or knee joint cooling seems to neither alter vertical jump height nor change movement biomechanics during two-legged jumping and landing.
... The dermis is characterized by the presence of a higher number of cold receptors (10-fold higher) in comparison to heat receptors. The current view is the following after a WBC/PBC exposure: vasoconstriction that is induced after cold exposure may play a role in decreasing the amount of blood in and around the muscles and in some organs (Charkoudian, 2003), in decreasing the cell permeability and leaking, in diminishing the fluid diffusion in interstitial space that can occur after physical exercise to reduce edema development, and in reducing inflammation (Banfi et al., 2009b). In the context of recovery after physical exercise, a WBC/PBC exposure induces a lower muscle temperature that may decrease muscle enzyme activities, metabolism, inflammation, and secondary degradation after hypoxia (lowering ischemia/reperfusion problems) that may help recovery (Bouzigon et al., 2016). ...
... The dermis is characterized by the presence of a higher number of cold receptors (10-fold higher) in comparison to heat receptors. The current view is the following after a WBC/PBC exposure: vasoconstriction that is induced after cold exposure may play a role in decreasing the amount of blood in and around the muscles and in some organs (Charkoudian, 2003), in decreasing the cell permeability and leaking, in diminishing the fluid diffusion in interstitial space that can occur after physical exercise to reduce edema development, and in reducing inflammation (Banfi et al., 2009b). In the context of recovery after physical exercise, a WBC/PBC exposure induces a lower muscle temperature that may decrease muscle enzyme activities, metabolism, inflammation, and secondary degradation after hypoxia (lowering ischemia/reperfusion problems) that may help recovery (Bouzigon et al., 2016). ...
... For instance, several studies highlighted that exposure to extremely low temperatures leads to a decrease in oxidative stress and reduces the inflammatory response. 18 Using a randomized controlled trial design, this study evaluated the impact of two different doses of WBC on the smelling capacities of former COVID-19 French patients. The first intervention required patients to take two sessions of WBC over one working week. ...
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The article entitled, "Whole-Body Cryotherapy as an Innovative Treatment for COVID 19-Induced Anosmia-Hyposmia: A Feasibility Study," by Legrand FD, Polidori G, Beaumont F, Bouchet B, Morin A, Derruau S, and Brenet E (Epub ahead of print Jan 13, 2022; DOI: 10.1089/jicm.2021.0254) is officially retracted at the request of the authors. This request came after the paper had undergone full peer review, three rounds of revisions, acceptance, page proofs, and ultimately, online publication. The Methods section of the published paper states that the study had "secured University ethics clearance…"1 but the authors explained that, "after re-discussion and internal reassessment, it appears clearly that this study required, according to French law, the approval of a specific committee known as the '[C]ommittee for the [P]rotection of [P]ersons (CPP)' and not a simple ethical agreement. For this reason, [we] request, in good faith, that the article be retracted. We apologize for this delay in taking a position, but this study gave rise to a re-discussion with our peers of the methodology which led us to realize our error 'a posteriori.'". The authors' respective institutions have been notified by the publisher. Journal of Integrative and Complementary Medicine is committed to upholding the rigors of scientific publishing and the veracity of the literature. Reference 1. Legrand FD, Polidori G, Beaumont F, et al. Whole-body cryotherapy as an innovative treatment for COVID 19-induced anosmia-hyposmia: a feasibility study. Epub ahead of print Jan 13, 2022; DOI: 10.1089/jicm.2021.0254.
... It was concluded that the stress-inducing noninfectious stimuli, such as repeated cold-water immersions, increased metabolic rate due to shivering and the elevated blood catecholamine concentrations of catecholamines, activating the immune system to a slight extent. Banfi et al. [33] studied the effects of systemic cold (cryogenic chamber), inter alia, the immunological parameters of athletes (IgM, IgG, IgA). The obtained results showed no change compared with the baseline measurements. ...
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Regular exposure to a cold factor—cold water swimming or ice swimming and cold air—results in an increased tolerance to cold due to numerous adaptive mechanisms in humans. Due to the lack of scientific reports on the effects of extremely low outdoor temperatures on the functioning of the human circulatory system, the aim of this study was to evaluate complete blood count and biochemical blood indices in multiple Guinness world record holder Valerjan Romanovski, who was exposed to extremely cold environment from −5 °C to −37 °C for 50 days in Rovaniemi (a city in northern Finland). Valerjan Romanovski proved that humans can function in extremely cold temperatures. Blood from the subject was collected before and after the expedition. The subject was found to have abnormalities for the following blood indices: testosterone increases by 60.14%, RBC decreases by 4.01%, HGB decreases by 3.47%, WBC decreases by 21.53%, neutrocytes decrease by 17.31%, PDW increases by 5.31%, AspAT increases by 52.81%, AlAT increase by 68.75%, CK increases by 8.61%, total cholesterol decreases by 5.88%, HDL increases by 28.18%. Percentage changes in other complete blood count and biochemical indices were within standard limits. Long-term exposure of the subject (50 days) to extreme cold stress had no noticeable negative effect on daily functioning.
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While the recent literature on Whole-Body Cryotherapy pointed to its beneficial systemic effects on inflammatory markers in rheumatoid arthritis, it was not clear whether it could also have more localized effects, with the attainment of analgesic thresholds on hands that are usually protected during protocols. Twenty-five young, healthy subjects (12 males aged 25.1 ± 3.5 years and 13 females aged 23.5 ± 2.6 years) agreed to participate in this study. Two study groups were defined: (1) a control group with a hand fully gloved and (2) an experimental group with a partially ungloved hand during the WBC session. In both groups, the achievement of analgesic thresholds of skin temperature was established through thermal imaging, focused on the measurement of temperatures at the different joint locations. Using a new protocol with direct exposure of the hands during the last 40 s of a standard WBC session of 3 min at −110 °C made it possible to respect this risk/benefit balance. Infrared thermography analyses revealed that for all regions of interest (except MCP and IP, CMP for thumb), there was a clinically meaningful reduction of skin temperature in participants from the experimental group. The thermal analysis suggests that a protocol of Whole-Body Cryotherapy at −110 °C where hands must be ungloved during 40 s could be a useful tool for the management of hand rheumatoid arthritis by achieving local antalgic thresholds.
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Partial body cryotherapy cabins most often use liquid nitrogen as their cryogenic fluid, which raises safety concerns during operation. In this study, an innovative cryotherapy cabin design is presented, featuring an electric cooling system suitable for producing cold air at −30 °C. The geometry of the designed cryotherapy cabin is evaluated by a thermodynamic modeling which aims at optimizing the circulation of cold air flows inside the cabin. The numerical study is carried out in two successive phases, the first one being necessary to model the pre-cooling phase and to estimate the time required to reach an average temperature close to the set temperature of −30 °C. The second one aims at modeling a 3-min cryotherapy session by taking into account the thermal transfers between the human body and its environment. Results demonstrate the potential benefits of the cold air injection device which has been designed to optimize the thermal transfers and homogenize the temperatures within the therapeutic enclosure. The main innovation of this study is the ability to customize cryotherapy protocols by injecting cold air at different levels through targeting of specific body areas. Further calculations would be required to determine the precise impact of zone-targeted injection on skin cooling.
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Athletes, military personnel, fire fighters, mountaineers and astronauts may be required to perform in environmental extremes (e.g. heat, cold, high altitude and microgravity). Exercising in hot versus thermoneutral conditions (where core temperature is ≥1°C higher in hot conditions) augments circulating stress hormones, catecholamines and cytokines with associated increases in circulating leukocytes. Studies that have clamped the rise in core temperature during exercise (by exercising in cool water) demonstrate a large contribution of the rise in core temperature in the leukocytosis and cytokinaemia of exercise. However, with the exception of lowered stimulated lymphocyte responses after exercise in the heat, and in exertional heat illness patients (core temperature >40°C), recent laboratory studies show a limited effect of exercise in the heat on neutrophil function, monocyte function, natural killer cell activity and mucosal immunity. Therefore, most of the available evidence does not support the contention that exercising in the heat poses a greater threat to immune function (vs thermoneutral conditions). From a critical standpoint, due to ethical committee restrictions, most laboratory studies have evoked modest core temperature responses (<39°C). Given that core temperature during exercise in the field often exceeds levels associated with fever and hyperthermia (>39.5°C) field studies may provide an opportunity to determine the effects of severe heat stress on immunity. Field studies may also provide insight into the possible involvement of immune modulation in the aetiology of exertional heat stroke (core temperature >40.6°C) and identify the effects of acclimatisation on neuroendocrine and immune responses to exercise-heat stress. Laboratory studies can provide useful information by, for example, applying the thermal clamp model to examine the involvement of the rise in core temperature in the functional immune modifications associated with prolonged exercise. Studies investigating the effects of cold, high altitude and microgravity on immunity and infection incidence are often hindered by extraneous stressors (e.g. isolation). Nevertheless, the available evidence does not support the popular belief that short- or long-term cold exposure, with or without exercise, suppresses immunity and increases infection incidence. In fact, controlled laboratory studies indicate immuno-stimulatory effects of cold exposure. Although some evidence shows that ascent to high altitude increases infection incidence, clear conclusions are difficult to make because of some overlap with the symptoms of acute mountain sickness. Studies have reported suppressed cell-mediated immunity in mountaineers at high altitude and in astronauts after re-entering the normal gravity environment; however, the impact of this finding on resistance to infection remains unclear.
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The blood pressure responses to an acute and long-term (three months) whole-body cryotherapy (WBC) were measured in men and women. Acute cold exposure (−10°C, −60°C, −110°C) increased both systolic and diastolic blood pressures temporarily. Neither significant gender differences nor adaptation in blood pressures were found during WBC. The variation of individual responses to the acute and long-term WBC was wide.
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The aim of this study was to investigate whether or not the human immune system can be activated by a noninfectious stimulus, thereby improving the physiological status of the individual. The effect of a single cold water immersion (14 degrees C for 1 h) on the immune system of athletic young men, monitored immediately after immersion, was minimal. With the continuation of the cold water immersions (three times a week for a duration of 6 weeks) a small, but significant, increase in the proportions of monocytes, lymphocytes with expressed IL2 receptors (CD25) and in plasma tumour necrosis factor alpha content was induced. An increase in the plasma concentrations of some acute phase proteins, such as haptoglobin and haemopexin, was also observed. After 6 weeks of repeated immersions a trend towards an increase in the plasma concentrations of IL6 and the amount of total T lymphocytes (CD3), T helper cells (CD4), T suppressor cells (CD8), activated T and B lymphocytes (HLA-DR) and a decrease in the plasma concentration of alpha 1-antitrypsin was observed. Concentrations of IL1 beta, neopterin, C-reactive protein, orosomucoid, ceruloplasmin, macroglobulin, immunoglobulins (IgG, IgM, IgA) and C3, C4 components of the complement, as well as the total number of erythrocytes, leucocytes, granulocytes and neutrophils showed no significant changes after the repeated cold water immersions. It was concluded that the stress-inducing noninfectious stimuli, such as repeated cold water immersions, which increased metabolic rate due to shivering the elevated blood concentrations of catecholamines, activated the immune system to a slight extent. The biological significance of the changes observed remains to be elucidated.
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This study examined the immunological responses to cold exposure together with the effects of pretreatment with either passive heating or exercise (with and without a thermal clamp). On four separate occasions, seven healthy men [mean age 24.0 +/- 1.9 (SE) yr, peak oxygen consumption = 45.7 +/- 2.0 ml. kg(-1). min(-1)] sat for 2 h in a climatic chamber maintained at 5 degrees C. Before exposure, subjects participated in one of four pretreatment conditions. For the thermoneutral control condition, subjects remained seated for 1 h in a water bath at 35 degrees C. In another pretreatment, subjects were passively heated in a warm (38 degrees C) water bath for 1 h. In two other pretreatments, subjects exercised for 1 h at 55% peak oxygen consumption (once immersed in 18 degrees C water and once in 35 degrees C water). Core temperature rose by 1 degrees C during passive heating and during exercise in 35 degrees C water and remained stable during exercise in 18 degrees C water (thermal clamping). Subsequent cold exposure induced a leukocytosis and granulocytosis, an increase in natural killer cell count and activity, and a rise in circulating levels of interleukin-6. Pretreatment with exercise in 18 degrees C water augmented the leukocyte, granulocyte, and monocyte response. These results indicate that acute cold exposure has immunostimulating effects and that, with thermal clamping, pretreatment with physical exercise can enhance this response. Increases in levels of circulating norepinephrine may account for the changes observed during cold exposure and their modification by changes in initial status.
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A limited number of experiments have shown that treatment of rheumatoid arthritis by means of cooling the entire body in cryogenic chamber reduces the pain in joints affected by inflammatory process and increases their mobility. The aim of the present thesis was to try explain the mechanisms responsible for the observed improvement of the patients' condition, and an investigation of the treatment's effect on selected hemodynamic indices. Tests were carried out on 63 patients with rheumatoid arthritis mainly in the 3rd and 4th stage of illness, all of whom had been treated for 14 days, once daily, by cooling the body for two-minute periods in cryogenic chamber with temperatures ranging from -110 degrees C to -160 degrees C, followed by kinesitherapy. It was demonstrated that after a single session in the cryogenic chamber, after 7 and 14 days the level of ACTH, cortisol and beta-endorphins in blood serum rises. The level of TSH, T4, T3, GH and 6-keto-PGF1 alpha+, however, remains unchanged. The cryogenic chamber treatment does not affect the heart rate, arterial blood pressure nor the value of the left ventricle fractional shortening index and its ejection, neither does it cause of arrhythmias and ischemic changes of the heart.
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Crude synovial collagenase, an enzyme that may affect joint cartilage in rheumatoid arthritis, can destroy whole articular cartilage. To study this phenomenon under more specific conditions, we purified collagenase synthesized by primary cultures of rheumatoid synovium and used it to degrade collagen fibrils purified from human articular cartilage. These highly cross-linked fibrils were resistant to solubilization in acetic acid-pepsin extracts and, in comparison with skin collagen fibrils reconstituted without intermolecular cross-links, were somewhat resistant to the collagenase as well. However, the rate of cartilage collagen lysis was affected by changes in reaction temperature. At temperatures found within rheumatoid knee joints (36°C) collagenolysis was four times greater than at temperatures found in normal knee joints (33°C). Part of the benefit from anti-inflammatory therapy in rheumatoid arthritis may be secondary to decreasing intra-articular temperatures, thereby decreasing the rate a...
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The cytokine response after thermal stress (sauna + swimming in ice-cold water) was investigated in subjectively healthy persons. Two groups were studied at the end of the winter season: habitual and inexperienced winter swimmers. Blood was collected at rest, after a sauna bath and after a short swim in ice-cold water. Conventional methods and ELISA kits were used to determined the blood picture, serum cortisol and dehydroepiandrosterone sulphate, plasma anti-diuretic hormone (ADH) levels, and the levels of several cytokines in plasma and in the supernatants of blood cell cultures which were stimulated with lipopolysaccharide (LPS). In regular winter swimmers, the concentrations of plasma interleukin 6 (IL-6), leukocytes, and monocytes at rest were significantly higher than in inexperienced subjects. In experienced female winter swimmers, the plasma concentration of the soluble receptor for IL-6 was significantly lower than in inexperienced female swimmers. In both groups, granulocytosis, haemoconcentration and significant increases in the concentrations of ADH, cortisol and IL-6 were observed after the stimuli. However, the changes in the cortisol concentration were dramatically larger in habitual winter swimmers. A significant correlation was found between the delta values of cortisol and the basal concentrations of IL-6. In cell cultures, the LPS-induced release of IL-1beta and IL-6 was higher at rest in the inexperienced winter swimmers. This release was dramatically suppressed after exposure to the stimuli in the inexperienced winter swimmers but tended to increase in the regular winter swimmers. These stresses appear to challenge both the neuro-endocrine and the immune systems and the results indicate that adaptive mechanisms occur in habitual winter swimmers.
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The effect of a year's isolation in Antarctica on the human mucosal immune system was assessed during the winter of 1992 at three Australian Antarctic stations: Casey, Davis and Mawson. Saliva samples were collected from each expeditioner prior to their departure from Australia and during each month in Antarctica. The concentrations of salivary immunoglobulins IgA and IgG were significantly different between the three stations, but there were no differences for salivary IgM and albumin. The mean concentrations of IgA were higher at Mawson (P < 0.008), and the mean concentrations of IgG were lower at Davis (P < 0.001) compared with the other stations. Ranges of values observed at the stations over the 12-13 months were similar. The variability of values within individuals showed station differences for salivary IgM and IgG only. The study revealed significant changes in salivary immunoglobulin values over the period in Antarctica, with similar patterns at the three Australian stations. The salivary IgA and IgM levels were lower in the first 4 months in Antarctica (January-April) and increased to maximum values in July-August, before returning to mean levels when isolation was broken in October-November. The patterns of salivary IgA and IgM suggest that stressors due to isolation may play a role in alterations of mucosal immunity in expeditioners in Antarctica.
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The purpose of this study was to characterize the extent of immune, endocrine, substrate and metabolic changes during a long-distance cross-country ski race in extremely well-trained athletes and evaluate if the blood perturbations would indicate signs of health risk. Ten male (M) and six female (F) national team skiers were investigated as they followed their usual routines of race preparations. Blood samples were drawn before and immediately after a World Cup 50-km M and 30-km F ski race with a mean finish time of 142 and 104 min, respectively. Hemoglobin, electrolytes, and C-reactive protein remained unchanged for both M and F. Serum testosterone remained unchanged in M, but doubled in F. Significant increases were observed in concentrations of granulocytes (F: 5 x, M: 5 x), natural killer cells (F: 2 x, M: 1.5 x), adrenaline (F: 12 x, M:10 x), noradrenaline (F: 7 x, M:5 x), growth hormone (F: 30 x, M: 2 x), cortisol (F: 1.5 x, M:2 x), glucose (F: 2 x, M:1.5 x), creatine kinase (F: 2 x, M:2 x), uric acid (F: 1.5 x, M: 1.5 x) and non-organic phosphate (F:2 x, M:2 x), while insulin concentration decreased (F: 0.5x, M: 0.8 x). Free fatty acid (FFA) concentration increased (F:2 x, M: 3 x). In conclusion, we observed substantial changes in several immuno-endocrine, substrate and metabolic measurements after long distance cross-country ski racing and suggest that some of these marked changes may reflect the large amount of muscle mass involved during skiing.
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s: The impairment of cardiac contractility during endotoxemia involves induction of nitric oxide formation through a cascade of events initiated by overexpression of proinflammatory cytokines. We previously showed that hypothermia attenuates endotoxin-induced overexpression of nitric oxide in rat lungs. In the present study, we tested the hypothesis that hypothermia protects against endotoxin-induced myocardial inflammation by changing the balance of pro- and anti-inflammatory cytokines, inhibiting myeloperoxidase, an indicator of neutrophil activity, and inhibiting nitric oxide-mediated protein damage. Rats were randomized to treatment with either hypothermia (n = 6; 18 to 24 degrees C) or normothermia (n = 6; 36 to 38 degrees C). Endotoxin (15 mg/kg) was administered intravascularly to anesthetized animals, and heart tissue was harvested 150 min later. Using enzyme-linked immunosorbent assays (ELISAs), we found that hypothermia induced myocardial expression of the anti-inflammatory cytokines interleukin (IL)-4 and IL-10, while decreasing concentrations of the pro-inflammatory cytokines IL-1beta and growth-related oncogene/cytokine-induced neutrophil chemoattractant (rat homolog of IL-8). Electromobility shift assay revealed that hypothermia inhibited the nuclear translocation of nuclear factor-kappaB. Reverse transcriptase-polymerase chain reaction and Western blot assays revealed that hypothermia attenuated the endotoxin-induced overexpression of both inducible nitric oxide synthase (iNOS) messenger RNA and iNOS protein, respectively. Hypothermia also attenuated nitric oxide-mediated myocardial protein damage, as determined by a nitrotyrosine ELISA. Myocardial myeloperoxidase content, an indicator of neutrophil accumulation and oxidative activity, was also inhibited by hypothermia in endotoxemic rats. These data demonstrate that hypothermia induces an anti-inflammatory cytokine profile, inhibits neutrophil aggregation, and inhibits the formation of nitric oxide during endotoxemia in the rat.