Transcript Effects of Spa Therapy on Inflammation and Immune System

Effects of Spa therapy on antioxidative status, inflammation,
immune system
Prof. Dr. M. Zeki Karagülle
Symposium on Research in Spa Medicine
Aix-les-Bains - November 17th 2006
Bourget lake
Practical
Exceptional
Famous
information
surroundings
residents
Microclimate
Ports
Department of Medical Ecology & Hydroclimatology
Istanbul Medical Faculty, Istanbul University
Spa therapy and Balneotherapy
• Do they have biologic effects on
Immune system and Inflammation
• and Oxidation ?
• Which mechanisms and mediators
are involved?
Terminology
• Spa therapy ; a complex intervention at a
spa resort, (balneotherapy + others)
• Balneotherapy ; Mineral/thermal water
therapy (Bathing + Drinking + Inhalation)
Inflammation
• the first response of the immune system to infection or
irritation characterised by the following quintet:
• redness (rubor),
• heat (calor),
• swelling (tumor),
• pain (dolor)
• dysfunction of the organs involved (functio laesa)
• The first four characteristics have been known since
ancient times and are attributed to Celsus; functio laesa
was added to the definition of inflammation by Rudolf
Virchow in 1858.
Immune System
A scanning electron microscope (SEM) image of a T-lymphocyte
(right), a platelet (center), and a red blood cell (left).
Image: The National Cancer Institute at Frederick
Inflammation
Chrousos G. N Engl J Med 1995;332:1351-1363
Cytokine Signaling Pathways Involved in Inflammatory Arthritis
Choy E and Panayi G. N Engl J Med 2001;344:907-916
Cytokines and Other Mediators of Inflammation That Influence the Hypothalamic-PituitaryAdrenal Axis
Chrousos G. N Engl J Med 1995;332:1351-1363
Spa- and Balneotherapy Studies on
Anti-oxidative status
• Anti-oxidant status in patients with Rheumatoid Arthritis
after Spa Therapy
M KARAGÜLLE, MZ KARAGÜLLE , O KARAGÜLLE, A
AVCI , İ DURAK
35th Congress of ISMH, June 6-10, 2006, Istanbul
• The Effect of Balneotherapy on Oxidant-Antioxidant
Systems in Primary Osteoarthritis
HN AKSOY, N ERDOĞAN, Ö AKSOY, GÖ ERATA, AH
KAYAR, MZ KARAGÜLLE
35th Congress of ISMH, June 6-10, 2006, Istanbul
Malondialdehyde (MDA) nmol/mL
SPA
Control
4
3,5
3
2,5
2
1,5
1
0,5
0
before
after
After 2-week spa
therapy;
• increased in SPA
group, decreased in
control group
• No statistically
significant change
intergroup (p=0.5)
and between group
(p=0.2) comparisons
Nonenzymatic Superoxide Radical
Scavenger Activity (NSSA) U/mL
SPA
Control
8,8
8,6
8,4
8,2
8
7,8
7,6
before
after
After 2-week spa
therapy;
• increased in both
groups
• Statisticaly significant
increase in SPA group
(p<0,05)
Antioxidant Defense Potential
(AOP) U/mL
SPA
Control
14
13,5
13
12,5
12
11,5
11
10,5
10
before
after
After 2-week spa therapy;
• increased in both groups
İn spa group agreater
extend but , not
statistically significant
Discussions
Increased levels of MDA (although not
statistically significant) suggests that;
• Per-oxidation reactions are accelerated
during or after spa therapy
• spa therapy may cause an extra oxidative
stress
Discussions
Increased levels of NSSA (statistically
significant) and AOP suggests that;
• antioxidant potential and activity are
improved
The Effect of Balneotherapy on Oxidant-Antioxidant
Systems in Primary Osteoarthritis
HN AKSOY, N ERDOĞAN, Ö AKSOY, GÖ ERATA, AH KAYAR, MZ
KARAGÜLLE
35th Congress of ISMH, June 6-10, 2006, Istanbul
• Decrease in MDA levels in patients with
high MDA levels
• Increase in MDA levels in patients with
low MDA levels
• Increase in TAA levels in male patients
• Decrease in TAA levels in females
(menopause-estrogens deficiency?)
The Effect of Balneotherapy on Oxidant-Antioxidant
Systems in Primary Osteoarthritis
HN AKSOY, N ERDOĞAN, Ö AKSOY, GÖ ERATA, AH KAYAR, MZ
KARAGÜLLE
35th Congress of ISMH, June 6-10, 2006, Istanbul
• Spa therapy decreases oxidant stress ?!
• Decrease in oxidant stress is more prominent
• Increase of antioxidant defence is less manifest
Free radicals and thermal water-controlled pilot study
T BENDER,G NAGY,J BARISKA,R VÁGHY,R GOMEZ,I KOVÁCS
4.Turkish-Hungarian Balneological Meeting, 25-26 January, Izmir, 2006
•
•
•
•
Patients: Spondylosis lumbalis N:30(10 in each group)
They got no NSAID and steroids, no other disease
Duration of the bath 30 minutes, at 34°C
Blood samples were taken before the first bath, after the
first bath and at end of 10 baths
MDA Protein
Debrecen
Mórahalom
Cserkeszölő
S
S
S
Glutathione
peroxidase
N.S
S
S
Superoxid
dismutase
N.S
S
S
Catalase
S
S
S
Free radicals and thermal water-controlled pilot study
T BENDER,G NAGY,J BARISKA,R VÁGHY,R GOMEZ,I KOVÁCS
4.Turkish-Hungarian Balneological Meeting, 25-26 January, Izmir, 2006
• There is difference between tap water and
mineral water therapy concerning the
effects on the free radicals
• The changes during tap water therapy
may be due to the thermal effect
• Effect of sulfur baths on antioxidative defense systems,
peroxide concentrations and lipid levels in patients with
degenerative osteoarthritis.
• Forsch Komplementarmed Klass Naturheilkd. 2002
Aug;9(4):216-20.
• Ekmekcioglu C, Strauss-Blasche G, Holzer F, Marktl W.
• Effect of 3-week spa therapy, two groups of
patients with and without sulfur baths
• Sulfur bath therapy could cause a reduction
in oxidative stress, alterations of SOD
activities
• [Effect of sulfur administration on lipid levels, antioxidant
status and peroxide concentration in health resort
patients] [Article in German]
• Forsch Komplementarmed Klass Naturheilkd. 2000
Apr;7(2):75-8.
• Scheidleder B, Holzer F, Marktl W.
• Effect of a 3-week spa therapy, two groups
of patients with and without drinking
sulphurous
• In both groups similar alterations of the
activities of antioxidative enzymes as well
as peroxide concentrations could be
detected.
Spa- and Balneotherapy Studies on
Inflammation, Immune System
•
•
•
•
Physiological effects studies in healthy subjects
In-vitro studies in cell cultures
Experimental (animal) models of arthritis studies
Therapeutic affects studies in patients groups;
ie in patients with rheumatic or dermatological
diseases
Experimental (animal) models of
arthritis studies
The decrease in paw volume in adjuvant injected paws at the end of
the experiment was the greatest in the sulfur group followed by tap
water group.
There was not any significant difference between the two experiment
and the control groups.
The chronic arthritis which developed in the non-injected left hind paws
reached maximum severity on the 9th day after CFA injection in tap
water and control groups and not before the 19th day in the sulfur
group.
Later on, edema in the sulfur group decreased statistically more rapidly
(p <0.001) compared to the other two groups.
Mud-bath applications reduced inflammation at day 20, at the end of the
treatment, the paw volume was significantly reduced in comparison to the
controls (p<0.01)
Indomethacin therapy caused a more rapid reduction of paw volume,
significant both at day 15 and at day 20 (p<0.05)
Studies in patient groups
• Rheumatic diseases
– Osteoarthritis
– Ankylosing Spondylitis
– Fibromyalgia
• Dermatological diseases
– Psoriasis
– Atopic dermatitis
Is immune system influenced in OA
patients by balneotherapy ?
Is immune system influenced in OA
by spa therapy
(mud pack + balneotherapy) ?
Is immune system influenced in
healthy subjects by spa therapy
(mud pack + balneotherapy) ?
• Why does a 3-week spa therapy, in
addition to drug treatment and weekly
group physical therapy alone, provide
beneficial effects that may last for at least
40 weeks, in patients with AS?
Answer can be found
• Why spa therapy in addition to medical
therapy has both short- and long-term
beneficial effects in female patients with
Fibromyalgia ?
Answer may be found
Conclusions
The results of the published clinical,
experimental, in-vitro and in-vivo studies
suggests that;
• Spa therapy and balneotherapy provide
• Anti-inflammatory
• Immunosuppressive
• Immunomodulatory
• Anti-oxidative
effects
Cytokines influenced by spa-and
balneotherapy
•
•
•
•
•
•
•
•
•
TNF-α
IL-1α
IL-1β
IL-6
IFN-γ
IL-2
IL-4
EGF
TGF- β1
Prostaglandines influenced by spaand balneotherapy
• PGE2
• Leukotriene; LTB4
• PGF2 α
Matrix Metalloproteinases
influenced by spa-and
balneotherapy
•
•
•
•
•
MMP-1
MMP-2
MMP-3
MMP-8
MMP-9
Cell Populations influenced by
balneotherapy
•
•
•
•
Langerhans cells
T- and B-cells
CD4+, CD4- cells
CD8+, CD8- cells
Others
• CRP
• Haptoglobuline
• Substance P
Conclusions
• There is high level (1A and 1B) clinical evidence
that spa therapy and balneotherapy are effective
interventions in the management of rheumatoid
arthritis, osteoarthritis, fibromyalgia and
ankylosing spondylitis,
• The mechanisms involved in this efficacy are
probably via cytokines and other inflammatory
mediators
• The anti-oxidative mechanisms may be also
involved !
Perspectives
• The favorable effects of spa and
balneotherapy on the cytokines and other
mediators of inflammation may create an
interesting future for these interventions in
the anti-cytokine / ‘‘biologic’’ therapy era.
Perspectives
• The favorable effects of spa and
balneotherapy on oxidative stress and
anti-oxidative status suggest that they may
have an important role to play in the
rheumatic diseases, as they lower the
oxidative stress and the resultant
inflammatory damage.
Conclusions
• These effects of balneo- and spa therapy
seems to differ among different patient
groups, but may be also different among
spa resorts, thermal/mineral waters used
and type of spa treatments provided
Questions to be answered
• What are the values of different mineral
waters and the specific chemical
constituents of mineral waters in observed
effects of balneotherapy on inflammatory
and oxidative processes?
Questions to be answered
• Do exercise, massage and other
therapeutic modalities administered during
spa therapy course besides
balneotherapy, contribute to the overall
favorable effects of spa therapy on
inflammation and immune processes?
Questions to be answered
• If yes, to what extend?
• And then, how many spa treatments
and/or what treatments when combined
with balneotherapy constitute the optimal
effect ?
Spa therapy and Balneotherapy
•
•
•
•
•
Do they have biologic effects
on Immune system and Inflammation
and Oxidation ?
Answer seems to be yes;
Which mechanisms and mediators
are involved?
• It is not completely understood yet
• in search of reaching a comprehensive
understanding of the ways and
mechanisms
• how the biomarkers, cytokines, hormones
and other mediators of inflammation and
immune system and oxidative stress and
anti-oxidation status are involved,
• and the roles they play in the effectiveness
of spa and balneotherapy
Merci de votre attention