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Influence of Cryogenic Temperatures on Inflammatory Markers in Patients with Ankylosing Spondylitis

Abstract

The aim of this study was to estimate the influence of cryogenic temperatures used for whole-body cryotherapy on inflammatory markers in patients with ankylosing spondylitis (AS) and healthy volunteers. The study involved 32 male persons: 16 patients with AS and 16 healthy volunteers. All subjects were exposed to a cycle of 10 daily procedures of whole-body cryotherapy at a temperature of -120°C lasting 2 minutes with subsequent kinesitherapy In both groups before and after a cycle of whole-body cryotherapy with subsequent kinesitherapy serum C-reactive protein, fibrinogen, mucoprotein, soluble intercellular adhesion molecule-1 levels and erythrocyte sedimentation rate were estimated. The results of this study indicate that cryogenic temperatures used for whole-body cryotherapy decrease level of inflammatory markers both in patients with ankylosing spondylitis and healthy volunteers.
Introduction
Ankylosing spondylitis (AS) is a chronic inflammatory
disease of the sacroiliac joints and the spine. The etiology
of AS is unknown. It is still not clear which precise mecha-
nisms determine the interactions between host factors
(HLA-B27 and other genes, cytokines, T lymphocytes) and
microbial factors leading to the manifestation and chronic-
ity of AS. Antigen HLA-B27 is found in only 6% of the
general population, but it occurs in approximately 93% of
individuals suffering from AS. AS is almost three times
more common in men than in women. It typically affects
young people, with beginning usually between 15 and 30
year of life. Chronic spinal inflammation can develop a
complete fusion of the vertebrae - a process called ankylo-
sis. Ankylosis causes total loss of mobility of the spine. AS
is also a systemic rheumatic disease. It can also produce
inflammatory process in peripheral joints of limbs, as well
as in several organs, as the eyes, heart, lungs and kidneys.
The main symptoms of the disease are pain and stiffness in
Polish J. of Environ. Stud. Vol. 19, No. 1 (2010), 165-173
Original Research
Influence of Cryogenic Temperatures
on Inflammatory Markers in Patients
with Ankylosing Spondylitis
and Healthy Volunteers
Agata Stanek
1
*, Grzegorz Cieślar
1
, Joanna Strzelczyk
2
, Sławomir Kasperczyk
3
,
Karolina Sieroń-Stoltny
1
, Andrzej Wiczkowski
2
, Ewa Birkner
3
, Aleksander Sieroń
1
1
Department and Clinic of Internal Diseases, Angiology and Physical Medicine,
Medical University of Silesia, Batorego 15, 41-902 Bytom, Poland
2
Department of Biology, Medical University of Silesia, Zabrze, Poland
3
Department of Biochemistry, Medical University of Silesia, Zabrze, Poland
Received: 28 April 2009
Accepted: 11 August 2009
Abstract
The aim of this study was to estimate the influence of cryogenic temperatures used for whole-body
cryotherapy on inflammatory markers in patients with ankylosing spondylitis (AS) and healthy volunteers.
The study involved 32 male persons: 16 patients with AS and 16 healthy volunteers. All subjects were exposed
to a cycle of 10 daily procedures of whole-body cryotherapy at a temperature of -120°C lasting 2 minutes with
subsequent kinesitherapy In both groups before and after a cycle of whole-body cryotherapy with subsequent
kinesitherapy serum C-reactive protein, fibrinogen, mucoprotein, soluble intercellular adhesion molecule-1
levels and erythrocyte sedimentation rate were estimated. The results of this study indicate that cryogenic tem-
peratures used for whole-body cryotherapy decrease level of inflammatory markers both in patients with anky-
losing spondylitis and healthy volunteers.
Keywords: cryogenic temperatures, whole-body cryotherapy, inflammatory markers, C-reactive pro-
tein, mucoprotein, soluble intercellular adhesion molecule-1
*e-mail: astanek@tlen.pl
the low back, upper buttock area, neck, and the remaining
regions of the spine. The onset of pain and stiffness is usu-
ally gradual and these symptoms progressively worsen over
months [1-7].
As pharmacotherapy is not sufficient to improve clini-
cal state of patients with AS, physiotherapy seems to be one
of the cornerstones to the successful long-term manage-
ment of AS. It is applied for three major reasons [8-14]:
to maintain or restore spinal mobility,
to maintain or improve posture,
to improve chest expansion.
One of the most efficient methods of physical medicine
used in the treatment of many diseases of the motional sys-
tem is cryotherapy using extremely low temperatures
(below –100°C) applied for a short time (2-3 minutes) to
stimulate physiological reactions of the human organism, in
order to make more effective pharmacological treatment
and kinesitherapy (Fig. 1) [15-20].
The action of cryogenic temperatures causes in human
organisms several favorable, physiological reactions as:
analgesic effect, neuro-muscular effect, anti-inflammatory
and antiedematous effect, as well as circulatory effect. The
actual indications for cryotherapy include among others:
autoimmunologic diseases of joints and periarticular tissues
(ankylosing spondylitis, rheumatoid arthritis, psoriatic
arthritis, myositis and fibromyositis), degenerative, post-
traumatic and overloading lesions of motional system,
fibromialgia, osteoporosis, gout, diseases of central nervous
system with muscular hypertension, disseminated sclerosis,
radicular syndromes, diseases of peripheral nervous sys-
tem, depressive syndromes and vegetative neurosis, as well
as vital restitution, assistance of endurance and force train-
ing and acceleration of post-exertion restitution in active
sportsmen [15-25].
As the mechanism of positive therapeutic effects of
cryotherapy are still not completely known, the aim of the
study was to examine the influence of cryogenic tempera-
tures used for whole body cryotherapy on markers of
inflammatory status in patients suffering from AS and
healthy volunteers.
Experimental Procedures
Patients
The research protocol has been reviewed and approved
by the Bioethical Committee of the Medical University of
Silesia in Katowice (permission No. NN-013-144/1/02)
and all analyzed subjects gave their informed, written con-
sent for inclusion in the trial.
The study involved 32 male persons: 16 patients with
ankylosing spondylitis (experimental group, mean age
47±4.7 years) and 16 healthy volunteers (control group,
mean age 43±3.9 years) with no significant difference in
mean age between them.
Criteria of Inclusion
All patients included to the trial fulfilled the modified
New York Criteria for definite diagnosis of AS, which serve
as the basis for the ASAS/EULAR recommendations [26].
According to modified New York Criteria (1984) the
radiographic presence of sacroiliitis is a necessary condi-
tion for diagnosis of AS.
Using routine plain x-ray examination, the severity of
sacroiliac joint disease is divided into 4 grades [27]:
grades I – non-specific blurring of joint margin;
grade II – loss of definition of the sacroiliac joint mar-
gins, partial bone bridging or pseudowidening, initial
joint space widening, followed by joint space narrowing
and the indistinctness of the sacroiliac joint;
grade III – numerous severe erosions, widening of joint
space, partial ankylosing and definite sclerosis on both
sides of the joint;
grade IV – ultimate fusion of the sacroiliac joint (com-
plete ankylosing).
The presence of sacroilitiis of a grade ≥II bilaterally or
grade III or IV unilaterally fullfills radiologic criterion for
the diagnosis of AS.
Aside from sacroiliitis, the patient must exhibit 1 of the
following 3 clinical criteria for a diagnosis of AS to be
established:
low-back pain and stiffness present for more than 3
months with palliation by exercise and no relief with rest,
limitation of lumbar spinal motion in sagittal and frontal
planes,
limitation of chest expansion relative to age-and sex-
matched individuals.
Definite ankylosing spondylitis is present if the radio-
logic criterion is present in addition to at least 1 clinical cri-
terion. Probable ankylosing spondylitis is present if three
clinical criterion are present alone or if the radiologic crite-
rion is present but no clinical criteria are present [26].
All patients with AS were HLAB27 positive and they
exhibited III and IV radiographic grade of sacroiliac joint
disease. They did not suffer from any other diseases and
had no associated pathologies.
They were exposed to whole-body cryotherapy proce-
dures during sanatorium treatment at Health Resort in
Goczałkowice Zdrój.
166 Stanek A., et al.
Cryotherapy
Reduced stimulus threshold
Analgesia Reduced tendon reflexes
Reduced pain Reduced muscular tone
Prolonged relaxation
Improvement of motion range
Physical rehabilitation (kinesitherapy)
Fig. 1. The therapeutic mechanisms of cryotherapy according to
Knight [17].
They had not taken non-steroidal and anti-inflammato-
ry drugs in the month before the cryotherapy treatment.
Healthy volunteers were qualified to a complex treat-
ment (called cryorehabilitation) including cryotherapy
(treated as an assisting component) and subsequent kine-
sitherapy in order to obtain biological renovation, resulting
in: leveling of the physical and psychological fatigues,
quickening of post-exertion regeneration, intensification of
muscle contraction force, as well as improvement of phys-
ical condition, proper motor function and general feeling.
They were exposed to whole-body cryotherapy proce-
dures at the same Health Resort in ambulatory conditions.
Criteria of Exclusion
All patients included into the trial had not any com-
monly accepted contraindications for cryotherapy as: intol-
erance of cold, cryoglobulinemia, Raynaud’s disease,
hypothyroidism (increasing a risk of hypothermia), acute
diseases of respiratory tract, neoplastic disease (due to
adaptative intensification of local blood supply), instable
angina pectoris, severe valvular heart defects (in stage of
insufficiency of circulation), cardiac failure, severe arrhyth-
mias, purulent-gangrenous skin lesions, vegetative neu-
ropathies (due to predisposition to hyperhidrosis), local
blood flow disturbances, cachexia and hypothermia, as well
as claustrophobia and mental diseases (due to inability to
comply with safety rules in cryogenic chamber) [15-20, 25,
28, 29].
Cryotherapy Procedure
All patients of both groups were exposed for 10 con-
secutive days to a cycle of whole-body cryotherapy proce-
dures lasting 2 minutes a day, with subsequent 60-minutes
lasting routine kinesitherapy.
The whole-body cryotherapy procedures were per-
formed in the Cryoflex chamber, which consists of two
compartments: the antechamber and the proper chamber.
The temperature in the antechamber was -60°C, whereas in
the proper chamber it reached -120°C. After adaptation
process in the antechamber lasting 30 s, subjects were
exposed to cryogenic temperatures for 2 minutes in the
proper chamber. During the procedure of whole-body
cryotherapy all subjects were dressed with swim suit, cot-
ton socks and gloves, wooden shoes as well as face and ear
guards. The subjects were walking around the chamber dur-
ing whole procedure of cryotherapy without touching each
other. The program of kinesitherapy was arranged individ-
ually for each subject. No complications or side effects of
cryotherapy exposure were observed.
Blood Samples Acquisition
On the first and last day of a cycle of whole-body
cryotherapy with subsequent kinesitherapy in subjects from
both groups the following markers of inflammatory process
were estimated: serum C-reactive protein (CRP), mucopro-
tein (the complex of α
1
acute phase proteins, consisting
mainly of α
1
-acid glycoprotein,
3-5
1
-glycoprotein, hapto-
globin, as well as several others, which is soluble in per-
chloric acid solution and precipitable by phosphotungstic
acid) and soluble intercellular adhesion molecule-1
(sICAM-1) levels, plasma fibrinogen concentration as well
as erythrocyte sedimentation rate (ESR).
Samples of whole blood (volume 5 ml) were drawn
from a basilic vein of each subject. A part of collected blood
samples was placed directly into tube with citrate in order
to determine erythrocyte sedimentation rate. The rest of
blood samples was decanted and centrifuged, and then sep-
arated heparinized plasma and serum, respectively, were
immediately stored at a temperature of -70º C until bio-
chemical analyses were made. Analyses were performed at
a temperature of 25ºC.
Laboratory Analyses
Serum CRP concentration was determined by means of
turbidimetric method using Photometric-turbidimetric Test
for the Quantitative Determination of human C-Reactive
Protein (CRP) in Serum and Plasma (Human Gesellschaft fűr
Biochemica and Diagnostica mbH, Germany) (λ = 340 nm)
[30]. For this method the linearity is kept up to 25 mg/dl
and the lower detection limit is 0.1 mg/dl. No prozone phe-
nomenon was observed up to 40 mg/dl. Reference values
for adults are up to 0.5 mg/dl.
Serum mucoprotein concentration was determined by
means of colorimetric method described by Winzler in
modification of De La Huerga et al. [31] using Kit pro-
duced by Aqua-Medica (Poland) and spectrophotometer
Specol (λ = 680 nm). For this method the reference values
for male range between 0.45 and 1.17 g/l.
Plasma fibrinogen concentration was determined by
means of modified Clauss method [32] using Multifibren U
Kit (Dade Behring Inc., USA) and multiparametric analyz-
er Kone Lap. For this method the measurement range lies
between 0.8 and 12 g/l. The precision of the method was
calculated with Control Plasma N and Control Plasma P for
5 days in 8-fold determination. The coefficient of variation
in the series was 2.9% and 7.2% for Control Plasma N and
control Plasma P, respectively. From day to day it was 1.6%
and 3.4% respectively. Normal reference values range
between 1.8 and 4.5 g/l.
Serum sICAM-1 concentration was determined by
means of enzyme-linked immunosorbent assay using
human sICAM-1 ELISA BMS201CE Kit (Bender
MedSystems GmbH, Austria) and absorption analyzer
PowerVave XS (Biotek, USA) (λ = 450 nm). For this
method the limit of detection for sICAM-1, defined as the
analyte concentration resulting in an absorption significant-
ly higher than the absorption of the dilution medium (mean
plus three standard deviations) was determined to be 3.3
ng/ml. The overall intra-assay coefficient of variation has
been calculated to be 4.1%, whereas overall inter-assay
coefficient of variation has been calculated to be 7.66%.
Influence of Cryogenic Temperatures... 167
According to manufacturer data the reference levels for
healthy blood donors ranged between 130 and 300 ng/ml.
Normal levels may vary depending on the collective serum
used, ranging up to 400 ng/ml.
Erythrocyte sedimentation rate (ESR) was measured by
means of standard method.
Statistical Data Analysis
The database was established in the software MS Excel
2000. Statistical analysis was undertaken using statistical
package Statistica 6.0 PL. For each parameter the indicators
of descriptive statistics were determined (mean value and
standard deviation SD).
The normality of the data distribution was checked
using the Shapiro-Wilk test, while the homogeneity of the
variance applying Levene test. In order to compare the dif-
ferences between control group and the AS group, indepen-
dent sample Student t test was used or alternatively Mann-
Whitney U test. Correlations between particular parameters
were statistically verified by means of Spearman’s non-
parametric correlation test.
Differences at the significance level of p<0.05 were
considered statistically significant.
Results
The obtained results are shown in Table 1 and Figs. 2-6.
In healthy volunteers initial vales of C-reactive protein,
mucoprotein, fibrinogen and s-ICAM-1 concentration as
well as erythrocyte sedimentation rate value were contained
within a range of reference values, though in case of
s-ICAM-1 they were close to the upper limit of the range.
In patients suffering from ankylosing spondylitis initial
values of C-reactive protein, mucoprotein, fibrinogen and
s-ICAM-1 concentration as well as erythrocyte sedimenta-
tion rate value were significantly higher (p<0.001) as com-
pared to control group of healthy volunteers.
After a cycle of cryotherapy procedures in patients with
ankylosing spondylitis a statistically significant decrease in
C-reactive protein concentration (6.37±8.09 and 2.17±4.31
mg/dl – before and after therapy, respectively, p=0.002)
(Table 1, Fig. 2), mucoprotein concentration (1.43±0.24 g/l
and 1.02±0.25 g/l – before and after therapy, respectively,
p<0.001) (Table 1, Fig. 3), fibrinogen concentration
(3.55±0.66 g/l and 2.98±0.72 – before and after therapy
respectively, p<0.001) (Table 1, Fig. 4), sICAM concentra-
tion (331±103 g/l and 262±76.9 – before and after therapy,
168 Stanek A., et al.
Parameter Group
Before cryotherapy
procedures with subse-
quent kinesitherapy
(mean value ± SD)
After cryotherapy
procedures with subse-
quent kinesitherapy
(mean value ± SD)
Statistical sig-
nificance
Serum CRP concentration
[mg/dl]
Ankylosing spondylitis 6.37 ± 8.09 2.17 ± 4.31 p=0.002
Healthy volunteers 0.00 ± 0.00 0.00 ± 0.00 p=0.00
Serum mucoprotein concentration
[g/l]
Ankylosing spondylitis 1.43 ± 0.24 1.02 ± 0.25 p<0.001
Healthy volunteers 1.06 ± 0.07 0.92 ± 0.14 p=0.002
Plasma fibrinogen concentration
[g/l]
Ankylosing spondylitis 3.55 ± 0.66 2.98 ± 0.72 p<0.001
Healthy volunteers 1.97 ± 0.58 1.71 ± 0.45 p=0.02
Serum sICAM-1 concentration
[ng/ml]
Ankylosing spondylitis 331.0 ± 103.0 262.0 ± 76.9 p=0.001
Healthy volunteers 290.0 ± 86.0 286.0 ± 81.2 p=0.836
Erythrocyte sedimentation rate
[mm/h]
Ankylosing spondylitis 19.19 ± 14.72 12.06 ± 11.06 p=0.001
Healthy volunteers 1.50 ± 0.63 1.13 ± 0.50 p=0.028
Table 1. Comparison of particular inflammatory markers values before and after the end of a cycle of whole-body cryotherapy proce-
dures with subsequent kinesitherapy in groups of patients with ankylosing spondylitis and healthy volunteers, with statistical evaluation.
0.0
2
.0
4
.0
6.0
8.0
10
.0
12
.0
14
.0
16
.0
Ankylosing spondylitis Healthy volunteers
C-reactive protein serum concentration [g/l]
before cryotherapy after cryotherapy
**
Fig. 2. Comparison of C-reactive protein (CRP) serum concen-
tration before and after a cycle of whole-body cryotherapy pro-
cedures with subsequent kinesitherapy in ankylosing spondyli-
tis group and control group of healthy volunteers.
*p<0.05, **p<0.01
respectively, p<0.001) (Table 1, Fig. 5), as well as in ery-
throcyte sedimentation rate (19.19±14.72 and 12.06±11.06
mm/h – before and after therapy, respectively, p=0.001)
(Table 1, Fig. 6) were obtained. Cryotherapy decreased sig-
nificantly mucoproteid concentrations (1.06±0.007 and
0.92±0.14 g/l – before and after therapy, respectively,
p=0.002) (Table 1, Fig. 3), fibrinogen concentration
(1.97±0.58 and 1.71±0.45 g/l – before and after therapy,
respectively, p=0.02) (Table 1, Fig. 4) and erythrocyte sed-
imentation rate (1.5±0.63 and 1.13±0.5 mm/h – before and
after therapy, respectively, p=0.028) (Table 1, Fig. 6) also in
the control group of healthy volunteers.
Discussion of Results
In the present study, before beginning of whole-body
cryotherapy cycle an increased CRP, mucoproteins, fibrino-
gen and sICAM-1 concentrations as well as elevated ESR
were observed in patients with ankylosing spondylitis as
compared to the control group. As a result of a cycle of
cryotherapy procedures a statistically significant decrease
in C-reactive protein, mucoproteins, fibrinogen and
sICAM-1 concentrations as well as ESR were found which
is indicative for anti-inflammatory effect. Cryotherapy
decreased significantly mucoproteins and fibrinogen con-
centrations as well as ESR also in the control group of
healthy volunteers.
The inflammatory response of tissues is associated with
vasodilatation, increased vascular permeability, recruitment
of immunologic cells, as well as the release of inflammato-
ry mediators and cytokines from these cells. The
macrophage-derived cytokines IL-1 and IL-6 are primarily
Influence of Cryogenic Temperatures... 169
0.00
0
.20
0
.40
0
.60
0.80
1
.00
1
.20
1
.40
1
.60
1
.80
Ankylosing spondylitis Healthy volunteers
Mucoprotein serum concentration [g/l]
before cryotherapy after cryotherapy
***
**
0.00
0.50
1.00
1.50
2.00
2.50
3.00
3.50
4.00
4.50
Ankylosing spondylitis Healthy volunteers
Fibrinogen plasma concentration [g/l]
before cryotherapy after cryotherapy
**
*
Fig. 3. Comparison of mucoprotein serum concentration before
and after a cycle of whole-body cryotherapy procedures with
subsequent kinesitherapy in ankylosing spondylitis group and
control group of healthy volunteers.
*p<0.05, **p<0.01, ***p≤0.001
Fig. 4. Comparison of fibrinogen plasma concentration before
and after a cycle of whole-body cryotherapy procedures with
subsequent kinesitherapy in ankylosing spondylitis group and
control group of healthy volunteers.
*p<0.05, **p<0.01, ***p≤0.001
0
50
100
150
200
250
300
350
400
450
500
Ankylosing spondylitis Healthy volunteers
s-ICAM-1 serum concentration [ng/ml]
before cryotherapy after cryotherapy
***
Fig. 5. Comparison of soluble intercellular adhesion molecule-
1 (sICAM-1) serum concentration before and after a cycle of
whole-body cryotherapy procedures with subsequent kine-
sitherapy in ankylosing spondylitis group and control group of
healthy volunteers.
*p<0.05, **p<0.01, ***p≤0.001
0.00
5.00
10
.00
15
.00
20
.00
25.00
30
.00
35
.00
40
.00
Ankylosing spondylitis Healthy volunteers
Erythrocyte sedimentation rate [mm/h]
before cryotherapy after cryotherapy
**
*
Fig. 6. Comparison of erythrocytes sedimentation rate in blood
before and after a cycle of whole-body cryotherapy procedures
with subsequent kinesitherapy in ankylosing spondylitis group
and control group of healthy volunteers.
*p<0.05, **p<0.01, ***p≤0.001.
responsible for the acute phase response, related to a pro-
tective change in plasma protein production by hepatocytes.
The main important acute phase proteins are C-reactive
protein (CRP), fibrinogen and mucoproteins. The erythro-
cyte sedimentation rate (ESR) is an index of the acute phase
response, mainly reflecting the concentrations of fibrinogen
and the α-globulins, but also other immunoglobulins, that
are not acute phase reactants. The acute phase markers most
frequently used as indicators of inflammatory activity in
patients with ankylosing spondylitis are ESR and CRP [33-
35].
Soluble intercellular adhesion molecule-1 (sICAM-1) is
a member of the immunoglobulin supergene family,
expressed on the surface of several cell types, including
leukocytes and endothelial cells [36, 37]. ICAM-1 is
induced on fibroblasts and endothelial cells by inflamma-
tory mediators such as IL-1, TNF-alpha and IFN-gamma. It
plays an important role in migration of leukocytes to the
sites of inflammation [38]. Elevated levels of sICAM-1 are
found i.e. both in serum [39, 40] and synovial tissue [41] in
patients with rheumatoid arthritis and they correlate with
the activity of the disease [39]. In patients with rheumatoid
arthritis a weak positive correlation between serum
sICAM-1 levels and serum CRP levels was confirmed [42].
The increased serum sICAM-1 levels were also observed in
patients with spondyloarthropathies and in these patients
positive correlations were found between sICAM-1 and
erythrocyte sedimentation rate, as well as serum C-reactive
protein and interleukin 6 levels, but not with serum TNF-
alpha level. These results suggest that sICAM-1 levels may
reflect the acute phase of inflammation [43].
The results obtained in present study show that whole-
body cryotherapy evokes anti-inflammatory effect in
objects exposed to its action.
Whole-body cryotherapy is a relatively new therapeutic
method of physical medicine with a history of about 20
years. Thus, research works on mechanisms of therapeutic
action of cryogenic temperatures are still carried on.
In available literature there are very few reports on the
influence of whole-body cryotherapy on inflammatory
markers in patients with inflammatory diseases of motion-
al system. So far the beneficial influence of whole-body
cryotherapy on this markers was confirmed only in our pre-
liminary study [23], in which 2-week lasting cycle of
whole-body cryotherapy procedures caused significant
decrease in serum C-reactive protein and seromucoid con-
centration.
On the other hand Banfi et al. [44] confirmed a slight,
but not significant decrease in serum C-reative protein con-
centration, significant decrease in serum sICAM-1 and pro-
inflammatory cytokines IL-2 and IL-8 levels, as well as
singnificant increase in anti-inflammatory cytokine IL-10
level in rugby players, who underwent a cycle of 5 daily
whole-body cryotherapy procedures during their regular
training.
It was also found that cold and exhausting exercise
modulate cytokine production, upregulating expression of
IL-6 and IL-1 receptor antagonist but downregulating IL-
1beta and TNF-alpha in monocytes of healthy men. These
changes in cytokine expression appear to be linked to
enhanced catecholamine secretion and subsequent c-AMP
production [45].
Taking into account the above data and the fact that in
present study the values of inflammatory parameters were
decreased by whole-body cryotherapy also in healthy vol-
unteers it seems that cryogenic temperatures could influ-
ence directly the immune response, probably through the
modification of IL-1beta, IL-2, IL6, IL8 and IL-10 release
from macrophages. The effect is beneficial in patients with
inflammatory diseases, but one can not exclude its potential
unfavourable influence on immune system in healthy sub-
jects.
One of the mechanisms of anti-inflammatory action of
whole-body cryotherapy may be linked to stabilization of
lysosome membranes and subsequent inhibition of release
of active enzymes from lysosomes [46]. It seems that this
effect could be related to increased ACTH and cortisone
blood concentrations, due to both whole-body cryostimula-
tion and physical training. It was observed in experimental
study that ACTH and cortisone modifies activity of lysoso-
mal enzymes in rats [47, 48]. It was also found that long
lasting physical training causes significant increase in cor-
ticosterone level as well as slight lowering of lysosomal
enzymes activity in rats [48].
In healthy individuals (men and women) after a single,
2-minute lasting cryostimulation a statistically significant
increase in the serum ACTH concentration without any sig-
nificant changes in cortisol level was observed [49].
Moreover in patients with rheumatoid arthritis exposed to a
cycle of whole-body cryotherapy procedures a statistically
significant increase in serum cortisol concentration was
reported after a single treatment as well as after 7 and 14
procedures accompanied by kinesitherapy [50].
However Woźniak et al. [51] did not observe any statis-
tically significant changes in serum cortisol concentration
neither after a single session of cryostimulation of untrained
men nor after 6 and 10 days of cryostimulation procedures
accompanied by training. The concentration of cortisol
increased significantly only after the first 6 days of training
without cryostimulation and remained at that level after the
tenth day of training. In other study [52] in healthy women
exposed to a cycle of whole-body cryotherapy applied 3
times a week for 12 weeks, the first session caused only
temporary, insignificant increase in plasma ACTH and cor-
tisol concentration. In weeks 4-12 plasma levels of these
hormones were significantly lower than in week 1, proba-
bly due to habituation, suggesting that cryostimulation does
not stimulate pituitary-adreanal cortex axis.
These contradictory results suggest that probably
increase in ACTH and cortisol levels is not the only mech-
anism of lysosomal membranes stabilization caused by
whole-body cryostimulation.
The other mechanism of anti-inflammatory action of
whole-body cryotherapy resulting in stabilization of lyso-
some membranes could be related to its beneficial influence
on antioxidant enzymes activity [53]. In own clinical study
we observed increased activities of antioxidant enzymes,
increase in a level of plasma total antioxidant status and
170 Stanek A., et al.
lack of changes in a level of malonedialdehyde MDA (lipid
peroxidation marker) in patients with ankylosing spondyli-
tis after a cycle of repeated whole-body cryotherapy proce-
dures [54]. However it should be emphasized that a single
session of whole-body cryostimulation could induce distur-
bances of prooxidant-antioxidant balance, in form of low-
ering of total oxidative status (TOS) and temporary
decrease in total antioxidative status (TAS) with subsequent
elevation on the next day, resulting in increasing oxidative
stress [55]. It is suggested that repeated exposures to cryo-
genic temperatures may cause adaptative changes in form
of increase in antioxidative capacity and antioxidant
enzymes activity, resulting in formation of prooxidant-
antioxidant balance at higher level, assisting antiinflamma-
tory effect and protecting tissues against increased genera-
tion of reactive oxygen species and oxidative stress caused
by training [56-58].
Clinical evaluation of patients involved in present study
confirmed more favorable subjective estimation of clinical
effects of whole-body cryotherapy with subsequent kine-
sitherapy comparing with separate kinesitherapy in all per-
sons exposed to this method of physiotherapy. In patients
with AS a clinical improvement was related mostly to sub-
sidence or considerable reduction of pain intensity and to
decrease in recurrence rate of pain syndrome, as well as to
reduction of neurotonia, relaxation and subsidence of sleep
disorders. In healthy volunteers exposed to whole-body
cryotherapy during biological revival process a clinical
improvement was related mostly to augmentation of physi-
cal efficiency, reduction of neurotonia, relaxation and sub-
sidence of sleep disorders [59].
Moreover in patients with AS a significant improve-
ment of spine mobility in form of an increase in the values
of thoracic spine mobility range measured in Otto’s test,
lumbar spine mobility range measured in Shobers test, res-
piratory chest expansion range, lumbar left-lateral and
right-lateral flexure range and cervical left-lateral and right-
lateral rotation range, as well as a decrease in the values of:
“finger-floor”, “occiput-wall” and “chin-thorax” dimen-
tions was observed. In patients exposed to whole-body
cryotherapy with subsequent kinesitherapy percentage
changes in the values of particular parameters were more
distinct as compared to patients in whom solely kinesither-
apy was used, mainly in case of lumbar and thoracic spine
mobility parameters [60].
Beneficial clinical effects of whole-body cryotherapy in
patients with AS as well as promising results of presented
laboratory report indicate the necessity of further studies in
order to find a final explanation of anti-inflammatory effect
of whole-body cryotherapy in patients with ankylosing
spondylitis.
Conclusion
Cryogenic temperatures used for whole-body cryother-
apy as a component of complex treatment decreases level
of inflammatory markers both in patients with ankylosing
spondylitis and healthy volunteers.
Acknowledgements
The project was supported by grant 3P05B156 25 from
the State Committee for Scientific Research, Republic of
Poland.
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... The observed changes of the parameters studied might be connected with reduction in oxidative stress, lipid profile parameters, or the anti-inflammatory action of WBC procedures [7,8,18,19]. ...
... In another paper Banfi et al. [17] presented that WBC procedures performed once daily for 5 days caused a rise of anti-inflammatory cytokine (IL-10) and a drop of proinflammatory cytokines (Il-2 and IL-8) in athletes. Moreover, the beneficial impact of WBC procedures on inflammatory parameters was also observed in patients with rheumatoid arthritis [33] and ankylosing spondylitis [7,34]. ...
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... Low temperature has an analgesic, anti-inflammatory, anti-swelling effect on the body, it also affects the circulatory, nervous, muscular and endocrine systems, as well as the rate of metabolic changes, which implies their use in disease entities related to these systems [1,3,4]. This method is used to relieve pain and inflammation in degenerative, neurological and rheumatoid diseases [5,6] as well as in the treatment of obesity [7] Among the numerous indications for cryotherapy, the use of cold treatment in patients with rheumatoid arthritis [8], fibromyalgia [9,10], ankylosing spondylitis [11,12] and multiple sclerosis [13] was the best documented. ...
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... Клінічна ефективність повітряної кріотерапії залежить від характеристик температурного впливу (інтенсивність, тривалість, періодичність впливу) та індивідуальних особливостей пацієнта (вид патології, вік, стать, переносимість низької температури). Для досягнення максимальної клінічної ефективності даного фізіотерапевтичного методу при проведенні курсового лікування багатьма авторами передбачаються різні підходи [1,2,3,12,16,17]. На сьогоднішній день проблема оптимального вибору періодичності та тривалості впливу екстремально низької температури на пацієнтів з больовими синдромами різної етіології залишається дискутабельною, вимагає подальшого вивчення і методологічного вдосконалення. ...
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Background: Ankylosing spondylitis (AS) is a chronic, inflammatory rheumatic disease. Due to the consequences of the disease, physiotherapy is considered to be an important part of the overall management of AS. Objectives: The objective of this review was to summarise the available scientific evidence on the effectiveness of physiotherapy interventions in the management of AS. Search strategy: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, AMED, CINAHL and PEDro up to February 2004 for all relevant publications, without any language restrictions. The reference lists of relevant articles were checked and the authors of included articles were contacted. Selection criteria: We included randomised and quasi-randomised studies with patients classified by the AS New York criteria and where at least one of the comparison groups received some kind of physiotherapy. The main outcomes of interest were pain, stiffness, spinal mobility, physical function and patient global assessment. Data collection and analysis: Two reviewers independently selected trials for inclusion, extracted data and assessed trial quality. Investigators were contacted to obtain missing information. Main results: Six trials with a total of 561 participants were included in this updated review as compared to three trials and 241 patients in the previous version. Two trials compared individualised home exercise programs with no intervention and reported low quality evidence for effects in spinal mobility (relative percentage differences (RPD) 37%) and physical function, in favour of the home exercise program. Three trials compared supervised group physiotherapy with an individualised home-exercise program and reported moderate quality evidence for small differences in spinal mobility (RPD 18%) and patient global assessment in favour of supervised group exercises. Finally, in one study a three week inpatient spa-exercise therapy followed by 37 weeks of weekly outpatient group physiotherapy (without spa) was compared with weekly outpatient group physiotherapy alone; there was moderate quality evidence for effects in pain (RPD 18%), physical function (RPD 24%) and patient global assessment (RPD 29%), in favour of the combined spa-exercise therapy. Reviewers' conclusions: The results of this review suggest that a home exercise program is better than no intervention, supervised group physiotherapy is better than home exercises, and that combined inpatient spa-exercise therapy followed by supervised outpatient weekly group physiotherapy is better than weekly group physiotherapy alone. The tendency toward positive effects of physiotherapy in the management of AS calls for further research in this field. New trials should also address other physiotherapy interventions commonly used in clinical practice.
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Trotz intensiver Forschungsanstrengungen der letzten 3 Jahrzehnte ist es derzeit noch immer ungeklrt, welche genauen Mechanismen der Interaktionen zwischen Wirtsfaktoren (HLA-B27, andere Gene, Zytokinmilieu, T-Zellen) und mikrobiellen Faktoren zur Entwicklung und Chronifizierung einer ankylosierende Spondylitis (AS) fhren. Neben der Entschlsselung immunologischer Prozesse ist es vor allem die Aufklrung von Knocheneubildung und Ankylose, welche Rheumatologen und Histopathologen beschftigt. Von groen genomweiten Analysen und Kandiatengen-Studien wird erwartet, dass neue, mit AS vergesellschaftete Gene und vor allem auch prognostisch interessante Allele (Aussagen ber Chronifizierung, Spontanverlauf, extraskelettale Manifestationen, Schweregrad des AS) gefunden werden.Despite intensive research during the last three decades, it is still not clear which precise mechanisms determine the interactions between host factors (HLA-B27 and other genes, cytokines, T lymphocytes) and microbial factors leading to the manifestation and chronicity of ankylosing spondylitis (AS). Rheumatologists and histopathologists have focused their interest on decoding the immune-mediated inflammatory processes and on studying new bone formation and ankylosis. Concerning the genetic basis of AS, there is considerable effort in large genome-wide and candidate gene analyses to discover new genes that are associated with AS. Moreover, such genetic studies could identify genomic regions that determine clinical manifestations and the course of disease.