Download Inflammation Regulation Drug Traumeel

Inflammation Regulation Drug
Traumeel
IAH AC Inflammation Regulation Drug
Traumeel
© IAH 2007
In this course Traumeel is presented as a new class of medication used to treat
inflammatory processes. In fact Traumeel is not a classical NSAID but an
Inflammation Regulating Drug. Argumentation for that is the basis for this lecture.
1
Physiological processes
• Most physiological processes in the human body are autoregulative
• Respiration
• Blood pressure
• Heart rhythm
• Defense system
• ….
• Auto-regulation is needed to adapt the organism’s reaction
versus changing impulses out of the proper body and
environment.
© IAH 2007
2
Most physiological processes in the human body are steered over auto-regulating
systems. Around an adaptable set point these systems will balance in a wave
pattern by alternating action of agonists and antagonists. Most steering activities
are induced over mediators like chemokines, hormones, interleukins, etc…
Examples of these auto-regulating systems are the blood pressure, heart rhythm,
defense activities, sleep-awake status, female cycle, muscle tonus, respiration
rhythm, and many others.
Autoregulation systems can be defined as biological systems equipped with
inhibitory feedback systems such that a given change tends to be largely or
completely counteracted. The forward output of such a system, will thus
immediately trigger the corresponding inhibitory system so that overshoot of the
process is prevented, and after the offending stimulus is removed, the system
can return to baseline
In the organism, trigger and feedback interactions are subtle, using micro or even
nano-dosages of mediators. Diseases can be defined as caused by deregulations
of these processes, important deviations of the set points or even completely
changed set points that are not purposeful anymore.
2
Auto-regulating systems in the body
• Have an adaptive set point
• Have positive or negative feed back systems to keep control
over the output
• Use agonists and antagonists to steer
• Are purposeful
• Can deregulate
• Can get rigid
© IAH 2007
3
Auto-regulating systems in the body have some remarkable characteristics. They
have an adaptive set point which means that the system will adapt to
circumstances and influences in a regulative way. By the feed back system wave
patterns of correction and adaptation are used to stay regulated as close as
possible to the set point. The wave pattern is continuous and in no way the
adaptation to a new circumstance is linear.
To steer the adaptation agonists and antagonists are used alternating in
overweight to ‘balance’ around the set point.
The auto-regulation systems are purposeful, which means that the energy used
to realize the objective is minimal for a maximal result.
Auto-regulating systems can deregulate or even block due to external influences
or false feed back information. Deregulated information streams will almost
always lead to disease.
3
The defense system is an autoregulation system to defend the
organism
© IAH 2007
An important example of a changed auto-regulation system in the body’s defense
is an inflammation. Inflammation is a cleansing process, mainly taking place at
the level of the extracellular matrix, trying to get rid of causal foreign or body own
toxins. To do this a mostly local mobilization of defense cells is created to attack
and eliminate the toxins.
4
Inflammation is an auto-regulated mainly local
manifestation of defense creating:
• Pain
• Swelling
• Redness
• Local temperature increase
• Loss of tissue function
© IAH 2007
5
The pain, swelling, redness, temperature increase and loss of the function of the
affected tissue (Calor, Rubor, Dolor, Tumor, and function loss or function laesae)
are only the expression and result of what is going on in the organism: a trial to
adapt defense regulation to the intoxicated status. At the same time that the
inflammatory mediators are secreted, the corresponding anti-inflammatory
mediators will be secreted so that the inflammatory and anti-inflammatory effect
will be balanced till homeostasis is once more reached after the disturbance is
dealt with.
5
The inflammation cascade
TH-0
antigen
APC
TH-1
TH-2
Cellular defense
CD8+
Humoral defense
BC
MF
© IAH 2007
EOP
MC
6
Inflammation is a complex process of enhanced defense that over diverse trigger
and regulation mechanisms is steered. Important in this is the fact that antigen
coming into the body quickly will be detected by antigen presenting cells (APC).
In the major histocompatibility complex class II (MHC-class II) of the APC
characteristic proteins of the antigen will be presented to trigger unspecific and
specific defense against this antigen. Pro-lymphocytes will become competent T
helper cells due to the fact that they ‘blueprint’ the MHC information of the APC.
In this way a TH-1 pathway is created that will take care of a stimulated cellular
defense, mainly by activation of macrophages and cytotoxic cells (cT cells or
CD8+ cells). Over this pathway damaged and by antigen intruded cells (e.g.
viruses) will be eliminated. On the other hand there is the creation of a TH-2
pathway out of the same MHC-information that will create and enhance a
humoral defense against the antigen. This is mainly done over B-cell activation,
triggering of eosinophiles and mast cell degranulation. The last one will, over the
release of histamine ameliorate defense transport and over the release of
phospholipids lead to the formation of pro-inflammatory mediators like
prostaglandins and leukotrines.
6
Conventional medicine inflammation approach
• Inflammation is seen as disease and should be inhibited by all
means
• Conventional anti-inflammatory medication blocks off the
regulation process that steers the cleansing activity of the
defense system
© IAH 2007
7
In conventional medicine inflammation is not seen as a cleansing or restoring
process but as the characteristic of a disease. Therefore it should be inhibited by
all means to regain health. The inflammation can be primary or secondary but the
conventional approach remains the same: anti-inflammatory medications are
used to block the cascade of the inflammation process.
7
Conventional medicine inflammation approach
• By using all kind of suppressing medication that intervenes in
the inflammatory process
• Common NSAID’s
• COX-II inhibitors
• 5-LOX inhibitors
• Corticoids
• Antihistaminica
• Mastcell stabilizers
•…
© IAH 2007
8
Most conventional medications used in inflammation have one characteristic in
common: in one way or another they block of a pathway of the inflammation
process. Blocked aspects can be an enzyme (e.g. cyclooxygenase, 5lipooxygenase,…) or a receptor (H1-blockers, mast cell blockers in hay fever,…).
Most common is the use of the broad range of NSAIDs and the more specific
class of the COX-II inhibitors.
Beside a suppression of the inflammation symptoms they all will intervene in the
regulation systems of the inflammation cascade and therefore deregulate the
natural process of defense that was meant to cleanse the body.
From homotoxicological point of view conventional anti-inflammatory medications
are pushing the organism from a fight to a deposition reaction which means that
causal homotoxins will ‘condensate’ in the extracellular matrix.
8
Main side effects of conventional NSAID’s
• Gastro-intestinal disorders
• Blood platelet aggregation inhibited (anti-tromboxane effect,
risks on bleedings)
• Renal impairment (can lead to sodium and water retention)
© IAH 2007
9
Blocking the COX pathway with NSAIDs will be compensated by the organism by
a higher LOX pathway (side effects: bronchial spasm due to higher leukotrines)
and problems with higher thrombotic rates due to an increase in tromboxanes
(COX-II problematic). As the organism tries by all means (all inflammatory
pathways and the metalloproteinases) to eliminate the causal intoxication, any
suppression of a pathway will be compensated by an increased other proinflammatory pathway like communicating vessels will show increased levels if
one of them has been suppressed.
The consequences of blocked inflammatory pathways and compensation by
other inflammatory pathways leads to gastro-intestional disorders and blood
platelet aggregation disturbances.
Some of the molecules used in conventional treatment of inflammation are
nephrotoxic and can lead to renal impairment.
9
Contraindications of conventional NSAID’s
• Severe heart failure
• Gastric and duodenal ulceration
• If hypersensitivity is present against ASA or any other NSAID
molecule
• In severe renal and hepatic impairment
• COX-II should be used with care in cardiac failure
© IAH 2007
10
Due to direct or side effects classical NSAIDs are contraindicated in severe heart
failure and gastric and duodenal ulceration.
Some people are hypersensitive, intolerant or allergic to acetyl salicylic acid or
other anti-inflammatory components used in NSAIDs and therefore should not
use these type of medications.
Due to neprotoxicity and hepatoyicity NSAIDs are contraindicated in severe renal
and hepatic impairment.
Especially the class of COX-II inhibitors should be used with care in cardiac
failure.
10
Homotoxicological definition of illness
• Diseases are the expression of biologically purposeful defense
mechanisms against endogenic and exogenic homotoxins, or
the expression of the organism’s effort to compensate for toxic
damages it has sustained.
© IAH 2007
11
From a homotoxicological point of view, illness is caused by the body’s reaction to the presence of
disruptive homotoxins. What we recognize as the clinical symptoms of illness is what surfaces
after the defense system has reacted to the threat. This means that illness is not the presence of
symptoms as such, since these should only be seen as proof of ongoing defense activity. As long
as clinical symptoms are only viewed as a threat to the quality of life of the patient and the entire
treatment is geared to the removal of these symptoms, the results will be superficial and we are
actually mortgaging the patient’s long-term health. A biotherapeutic treatment takes into account
the causative homotoxins and, by stimulating the body’s own defense system, will affect the actual
causes of the illness. Biotherapy is always a regulation therapy, and never a suppression therapy.
Purposeful: This term is extremely important in the homotoxicological definition of disease. It
means that the reaction of the defense system will be in proportion to the needs to reach the
target. This encompasses every regulation aspect homotoxicology is referring to. Mobilization of
defense will be at the level that is needed to reach the target which in most cases is the
elimination of the homotoxin and his negative interactive activity with the cell and his environment
and to restore homeostasis. The regulation of the level of activity is done over a complex
mechanism of autoregulating systems, interacting one another and this over many different
mediators and feedback systems. Most reactions of the defense system are purposeful, but
inappropriate reactions (unpurposeful) can occur and create diseases on their own. Auto-immune
diseases for example are an inappropriate reaction of the defense system. The immune system is
attacking body own tissues which under normal conditions would be tolerated instead of attacked.
The same is true for allergic reactions such as hay fever. The reaction of the defense system is
not in relationship to the danger of the aggressor (the dust or the pollen) and therefore not
purposeful.
11
Homotoxicological definition of inflammation
• Inflammation is the expression of biologically purposeful
defense mechanisms against endogenic and exogenic
homotoxins
© IAH 2007
12
In the same way we could define inflammation as an expression of biologically
purposeful defense. The inflammation process is meant to eliminate toxic burden
or damage and restore a healthy situation by local mobilization of defense cells.
12
Inflammation in antihomotoxic medicine
• Inflammation is a cleansing process by which homotoxins are
eliminated, mostly at the level of the extracellular space
• Inflammation is steered by auto-regulating systems
• The steering is mainly done over all kind of mediators
• Cytokines like interferons (e.g. IFN-γ,…), interleukins (e.g.
IL-2, IL-8,… and chemokines (TNF-α, TGF-β,…)
• Hormones (e.g. DHEA, cortisol,…)
• antihomotoxic medications intervene modulating in the
regulation process
© IAH 2007
13
So, to summarize, we can state that inflammation is a cleansing and restoring
process that is steered by auto-regulating systems. Steering is done over the
release of all kind of mediators like cytokines and hormones.
With antihomotoxic medications we intervene modulating in these steering
processes by stimulation or inhibition of the secretion of mediators by defense
active cells.
13
Disease Evolution Table: Inflammation
• Inflammation is the second phase
•
•
on the table
Left of the
Regulation/Compensation
Division
Where the defense system reacts
with regulation to intoxication
Inflammation
Phases
© IAH 2007
14
In the disease evolution table (DET) inflammation is the second phase after
enhanced excretion. In fact by regulating defense against the present homotoxins
the extracellular terrain of the patient is cleansed so that cell function is not
endangered anymore. All acute inflammations in different tissues and organs are
classified in this second phase. Suppression of the inflammation process will
push the patient to the next phase which is the deposition phase. In this third
phase the homotoxins are no longer eliminated but get stored in the extracellular
matrix where on long term they will obstruct or deregulate a proper cell function.
14
The Immunological Bystander Reaction (IMBR)
and antihomotoxic medications (Prof. H. Heine)
Antihomotoxic preparation
The D refers to different potentizations of
substances. D4 - D8 is a selection from a range
of D1 - D14
oral s. c.
nasal i. v.
aerosol i. m. Absorption
Macrophage
Processing
Mediators which
activate ground
regulation
Major
histocompatibility
complex (MHC)
Differentiation of the
T-cells into regulating
Th3 with motif
Motif formation
(5-15 amino acids)
Homing
Similarity recognition
(Simile principle)
regulatory
lymphocytes (Th3)
e.g.
inflamed
joint
T-cell
(prolymphocyte)
Immunoglobulinproducing B
lymphocytes
Lymph node
Organotropism
Histotropism
TGF-β
IL-4
IL-10
Suppresion of
the matching
Th1, Th2
Inflammation-promoting
lymphocytes (Th1, Th2)
Clone formation in lymph nodes
© IAH 2007
15
The immunological bystander reaction, a principle in modern immunology, was
used by Prof. Hartmut Heine to postulate the working mechanism of some low
concentrated organic components in antihomotoxic medications.
Prof. Hartmut Heine was a histologist and at the end of 1997 he published his
hypothesis of the “Immunological Bystander Reaction pathway”, a
pharmacodynamic model (proven in vitro) for organic substances in the range of
D1 to D14.
Heine’s model is very important. Minute molecular concentrations of organic
components, like in the formula of Traumeel, stimulate a TH-3 mediated
immunological reaction. The figure above explains Heine’s model.
Where an antihomotoxic agent with low potentized proteins is introduced into the
GRS (Ground Regulation System) antigen presenting cells and dendritic cells will
eliminate it over phagocytosis. Characteristic proteins are transported back to the
macrophage’s surface in the form of short amino acid chains. These presentation
is antigen characteristic and specific. It is presented as a ‘motive’ in the MHC
class II on the cell surface (MHC – Major Histocompatibility Complex).
15
The Immunological Bystander Reaction (IMBR)
and antihomotoxic medications (Prof. H. Heine)
Antihomotoxic preparation
The D refers to different potentizations of
substances. D4 - D8 is a selection from a range
of D1 - D14
oral s. c.
nasal i. v.
aerosol i. m. Absorption
Macrophage
Processing
Mediators which
activate ground
regulation
Major
histocompatibility
complex (MHC)
Differentiation of the
T-cells into regulating
Th3 with motif
Motif formation
(5-15 amino acids)
Homing
Similarity recognition
(Simile principle)
regulatory
lymphocytes (Th3)
e.g.
inflamed
joint
T-cell
(prolymphocyte)
Immunoglobulinproducing B
lymphocytes
Lymph node
Organotropism
Histotropism
TGF-β
IL-4
IL-10
Suppresion of
the matching
Th1, Th2
Inflammation-promoting
lymphocytes (Th1, Th2)
Clone formation in lymph nodes
© IAH 2007
16
These motifs or patterns are recognized by passing naïve T-lymphocytes, which
over their receptors will interact with them. So, over the TCRs (T cell receptors)
of their own and the motif presented by the APC there is an interaction. This
interaction is the signal for them to become TH-3 cells (regulating lymphocytes).
The new TH-3 cells will be transported to the closest lymph ganglion (homing)
where they will be identically multiplied (cloning). The activated TH-3 cells search
for inflammation promoting lymphocytes (TH-1, TH-2) in the inflammation area,
which motives are dependent on the foreign substances that triggered the
inflammation. The TH3-cell will look for lymphocytes with a similar motive. As
soon as the similarity is confirmed, the TH-3 cells immediately start with the
synthesis of highly active TGF-ß (Transforming Growth Factor ß), which will
decrease the activity of the TH-1 and TH-2 lymphocytes. The inhibition of the TH1 and TH-2 accuracy will result in an inhibition of the inflammation stimulation by
these lymphocytes, which will result in less inflammation symptoms and activity.
In one sentence we could state that Traumeel stimulates the creation of specific
TH-3 cells that by the release of TGF-β will inhibit the TH-1 and TH-2 activity.
16
3 action pathways known
NF-κβ
Traumeel
IL-1
TGF-β
TNF-α
© IAH 2007
17
Traumeel has inflammation regulating capacities and therefore is called an
inflammation regulating drug (IRD).
3 main pharmacokinetic pathways are known out of basic research. Components
of Traumeel will influence the nuclear transcription factor kappa beta (NF-κβ) in
this way that lesser pro-inflammatory genes are triggered to stimulate the
secretion of pro-inflammatory mediators out of the cell. Another action of
Traumeel is the inhibition of IL-1 and TNF- α, two strong pro-inflammatory
mediators that are down regulated. The third known pharmacokinetic action is by
stimulating the formation of specific Treg cells (TH-3 lymphocytes known as a
variant of CD4+ cells) that by the release of transforming growth factor beta
(TGF-β) will inhibit pro-inflammatory Th-1 and TH-2 cells.
17
3 action pathways known
Traumeel
TGF-β
© IAH 2007
18
Prof. H. Heine postulated that one of the main activities of Traumeel lies in its ability to stimulate the
production of specific TH-3 (T-regulating cells) that by the release of TGF-β will inhibit the activity of proinflammatory TH-1 and TH-2 cells[1].
Basic research to which forms the foundation to this postulation was the 1995 research of Prof. Weiner at
the University of Boston. He found out that specific proteins in high dosages will induce the production of
pro-inflammatory CD4+ T lymphocytes (TH-1 and TH-2 cells) whereas micro doses of this same protein will
induce the production of anti-inflammatory CD4+ T lymphocytes (Treg cells). This phenomenon is called
‘oral tolerance’ in immunology and refers to the fact that the organism is programmed to be tolerant if
exposed to minor quantities of a foreign protein (if not the body would react in defense to everything it
meets, in toxic quantities or not).
Heine did basic research on TGF-β production of small dosages of different proteins (plants and organ
extracts) in full blood cultures and his approach seemed to be confirmed for many of them. Although not all
proteins seem to trigger a TGF-β production, the main components of Traumeel do so.
TGF-β has two main effects that are extremely interesting to understand the therapeutic results we have
with Traumeel. As mentioned above, TGF-β will inhibit pro-inflammatory T cells with a similar motive on their
TCR as the Treg cell has.
Above that TGF-β has a strong stimulating effect on fibroblasts. Fibroblasts generate the proteoglycan (PG)
and glycosaminoglycan (GAG)-matrix at the level of the extracellular environment. Fibroblasts also repair
damaged collagen. During the shock phase of an inflammation (acid phase) the PG and GAG structure is
degraded but in the anti-shock phase the structure is repaired by the fibroblasts. TGF-β will directly stimulate
the fibroblast’s action and create a new matrix in a much shorter time. As the matrix is the basic structure for
wound healing this explains the value of Traumeel in wound healing and traumata of different origin.
As the matrix is also a biophysical filter that will select the transmission of substances traveling from the
capillaries to the cells and vice versa the quality of the life of the cell depends directly on the quality and
purity of that matrix. More than one reason enough to repair it faster when damaged by inflammation and to
keep it as pure as possible by accurate and purposeful defense.
[1] Heine H, Schmolz M. Immunologische Beistandsreaktion durch pflanzliche Extrakte in
Antihomotoxischen Präparaten. Biologische Medizin. 1998, 27 (1), 12-14.
18
3 action pathways known
Traumeel
IL-1
TNF-α
© IAH 2007
19
Other recent basic research[1] showed the inhibiting effect of Traumeel on IL-1β
and TNF-α. Both mediators are cortisol antagonists. In fact they are TH-1
mediated inflammation promoters as cortisol is the negative feedback mechanism
to IL-1 and TNF-α. In the balance of agonists and antagonists a IL-1β and TNF-α
inhibition will favor the cortisol effect which is an anti-inflammatory effect. Above
that new research shows that cortisol in fact has some of its peripheral antiinflammatory effect via the secretion of TGF-β .
It is clear that due to this effect we see a strong reduction of the clinical
symptoms in inflamed patients using Traumeel.
[1] Porozov S, Cahalon L Weiser M, Branski D, Lider O, Oberbaum M., Inhibition
of IL-1β and TNF alpha Secretion from Resting and Activated Human
Immunocytes by Homeopathic Medication Traumeel S. Clinical & Developmental
Immunology. 2004 ;11(2): 143-149.
19
3 action pathways known
NF-κβ
Traumeel
© IAH 2007
20
A particular role in the inflammation process is filled in by NF-κβ or the nuclear
transcription factor kappa beta. Free radicals, bacterial products and cytokines
bind to receptors on the cell wall and then will through a series of intermediate
messengers cause the release of NF κ B. NF-κβ will migrate to the cell nucleus
where it triggers the transcription of inflammatory mediators, such as IL 1 and
TNFα.
Components of the Traumeel formula (of the asteracea family) contain helenanin
which is a sesquiterpene lactone that strongly inhibits NF-κβ. So, we can
postulate that Traumeel directly also inhibits NF-κβ and over this inhibits the
release of pro-inflammatory cytokines by the cell.
This postulation fits with results from above mentioned basic research on
inhibiting effect of Traumeel on IL-1 and TNF-α. Both mediators are strong
inducers of NF-κβ migration to the nucleus. The inhibiting effect of IL-1 and TNFα has a synergic effect with the direct inhibition of NF-κβ by the helenanin
containing Traumeel components.
20
Traumeel stimulates TGF-β secretion
• Traumeel stimulates the formation of specific T-regulator cells
(TH-3: CD4+ inflammation inhibiting cells) that by the secretion
of TGF-β will inhibit the TH-1 and TH-2 cells (CD4+ proinflammatory T cells)
• TGF-β inhibits at the beginning of an inflammation cascade
(top: pro-inflammatory T-cells)
• TGF-β stimulates the activity of fibroblasts (matrix generation:
better tissue and wound healing)
© IAH 2007
21
As in the inflammation cascade Treg cells intervene with TGF-β to down regulate
pro-inflammatory CD4+cells, Traumeel components will regulate inflammation at
the top of the cascade. The higher in a chain reaction we intervene regulating,
the more parameters will be involved in that regulation.
21
The inflammation cascade
TH-0
antigen
APC
TH-1
TH-2
Cellular defense
CD8+
Humoral defense
BC
MF
© IAH 2007
EOP
MC
22
Inflammation is a complex process of enhanced defense that over diverse trigger
and regulation mechanisms is steered. Important in this is the fact that antigen
coming into the body quickly will be detected by antigen presenting cells (APC).
In the major histocompatibility complex class II (MHC-class II) of the APC
characteristic proteins of the antigen will be presented to trigger unspecific and
specific defense against this antigen. Pro-lymphocytes will become competent T
helper cells due to the fact that they ‘blueprint’ the MHC information of the APC.
In this way a TH-1 pathway is created that will take care of a stimulated cellular
defense, mainly by activation of macrophages and cytotoxic cells (cT cells or
CD8+ cells). Over this pathway damaged and by antigen intruded cells (e.g.
viruses) will be eliminated. On the other hand there is the creation of a TH-2
pathway out of the same MHC-information that will create and enhance a
humoral defense against the antigen. This is mainly done over B-cell activation,
triggering of eosinophiles and mast cell degranulation. The last one will, over the
release of histamine ameliorate defense transport and over the release of
phospholipids lead to the formation of pro-inflammatory mediators like
prostaglandins and leukotrines.
22
The inflammation cascade
TH-0
antigen
APC
TH-1
TGF-β
Cellular defense
CD8+
TGF-β
Humoral defense
TH-3
BC
MF
© IAH 2007
TH-2
EOP
MC
23
The TH-3 down regulation over TGF-β is seen on the picture above. TGF-β
inhibits TH-1 and TH-2 activity and is an important regulator in keeping the
inflammation process within reasonable limits. As shown on the picture this down
regulation is at the top of the inflammation cascade and not at the bottom as is
the fact in conventional medications like NSAIDs (prostaglandin-synthesisinhibitors).
23
TH0
DH
EA
Co
rti
s
ol
TH3
TH2
TH1
IL-2
IL-4, 13
IFN gamma
TGF-beta
IL-5
IL-10
TNF
Inflammation
© IAH 2007
Inhibition
Allergy
24
Pregnenolone and subsequently DHEA are called the mother of hormones by
researchers because it is used by the body to manufacture many other
hormones, including our sex hormones that are necessary for many body
functions (e.g. estrogen, testosterone, progesterone, cortisol,…) They are
responsible for the maintenance of many body functions such as fat and mineral
metabolism, controlling stress, maintaining male and female characteristics and
others. The body produces DHEA and then converts it on demand to these other
hormones.
DHEA stimulates cellular immunity or skewing of TH-1 mediated reaction in the
balance where as cortisol inhibits TH-1 reactions but will stimulate on long term
TH-2 mediated reactions. We can state that a long term secretion of cortisol (e.g.
stress) will induce a skewing at the TH-2 side of the balance inducing allergies,
some auto-immune diseases and even cancer. Some auto-immune diseases are
TH-1 driven (e.g. morbus Crohn)
As TH-3 regulator cells, over the release of TGF-β, inhibit both sides of the
balance (down regulation) it does not directly intervene in the dysbalance but in
the intensity of both the TH-1 or TH-2 expression.
We know from research1 that Traumeel inhibits the sectretion of IL-1β and TNFα. These two mediators inhibit cortisol production. That is why Traumeel has
such an infammation down regulating effect, amongst others.
1. Porozov S, Cahalon L Weiser M, Branski D, Lider O, Oberbaum M., Inhibition
of IL-1β and TNF alpha Secretion from Resting and Activated Human
Immunocytes by Homeopathic Medication Traumeel. Clinical & Developmental
Immunology. 2004 ;11(2): 143-149.
24
Inhibiting
Interleukines and other mediators
activating
NK-cells
dendritic
cells
IL-12
TH-2
F-β
TG
TH-3
Mast cells
TGF
IL-4
-β
Eosino-
IL-10
phile
TH-1
TH-2
IFN-γ
IL-2
IFN-γ
IL-2
IFN-γ
IFN
-γ/
TN
Fβ
IL-12
IL-4 IL-5
IL-3
IL-4
IL-6 IL-13
IL-10
B-cell
B-cell
cT-cell
IgG2a
activation
macrophage
activation
© IAH 2007
Mast cell
Other Ig
classes
growth
25
A large number of mediators regulate an immune response. Although both sides
of the TH1/TH2 balance induce different actions they both are able to ‘control’
and inhibit reciprocally their own actions. A TH1 mediated pathway will inhibit
over the release of interferon gamma the TH2 pathway and the other way around
the TH2 cell can over the release of interleukin 10 inhibit the TH1 pathway.
Above TH1 and TH2 stands the regulator cell (TH3 or Treg cell) that over the
release of transforming growth factor beta can inhibit both the TH1 and TH2
pathway.
In function of the cellular or humoral defense different immunocytes are
activated. In both pathways the activity of the ending cell in the cascade
influences the input of the pathway. Macrophages stimulate TH1 activity over the
release of IL-12 but are activated themselves by the release of IFN-γ and TNF-β,
both released by the TH1 cell. In this way a loop is created.
A similar loop is seen in the TH2 pathway. Mast cells induce TH2 activity that
over the release of Interleukin 3, 4 and 10 will activate the mast cell.
To conclude we can state that both the TH1 and TH2 pathways, over positive
feedback, stimulate their own loop which is only inhibited by the reciprocal
inhibition between TH1 and TH2 and the supervising regulating effect of the Treg
cells.
25
© IAH 2007
26
In an inflammation we see TH-1 and TH-2 pathways alternating around a set
point of balance. Desoxicortisol will stimulate a TH-1 state there as cortisol will
induce a TH-2 state. An overweight of one of the two will cause a prolonged
characteristic status of cellular or humoral defense with all the consequences
mentioned already before. Keeping the wave pattern moving until a harmonious
set point is reached or getting as close as possible to that is one of the targets of
immunomodulation.
The picture always explains the danger of the prolonged TH-1 blocking use of
corticoids in conventional therapy as this medication will push and keep the
patient into a TH-2 mediated defense with all his consequences.
26
Traumeel S inhibits pro-inflammatory cytokines
• Traumeel is proven to have strong inhibiting effects on IL-1β,
TNF-α and IL-8(1)
• IL-1β and TNF-α are pro-inflammatory cytokines that have a
strong antagonistic effect on cortisol
• By inhibiting IL-1β and TNF-α the effect of the body’s own effect
of cortisol becomes more pronounced.
1) Porozov S, Cahalon L Weiser M, Branski D, Lider O, Oberbaum M., Inhibition of IL-1β and
TNF alpha Secretion from Resting and Activated Human Immunocytes by Homeopathic
Medication Traumeel S. Clinical & Developmental Immunology. 2004 ;11(2): 143-149.
© IAH 2007
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Traumeel S inhibits nuclear transcription factors
• NF-κβ is a complex of nuclear transcription factors that under
the impulse of antigens migrates to the cell nucleus and triggers
specific genes to stimulate the cell to release pro-inflammatory
cytokines (like TNF-alpha)
• Asteracea in Traumeel S inhibits NF-κβ migration
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Traumeel indication
• Traumeel is suitable for the treatment of
• primary and secondary inflammations, especially of the
musculoskeletal system (arthritis, inflammatory aspect in
reactivated arthrosis, PHS, tendonitis,…)
• traumata of all kind
• sport injuries (bruises, distortions, sprains, micro-lesions after
•
performance,…)
damaged soft tissues
© IAH 2007
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Due to his inflammation regulating capacities Traumeel can be used for the
treatment of most primary and secondary inflammations. Although this broad
indication area Traumeel is mainly used for inflammations of the locomotorial
system. It is a great medication in the treatment of sport injuries as most of these
disorders will go together with inflammation. Above that, due to the micro and
nano dosages of the components, doping risks are excluded.
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Pharmacokinetics synthesis
• TGF-β inhibits both TH-1 and TH-2 mediated pro-inflammatory
pathways
• IL-1 and TNF-α are released due to inflammatory impulses
• Antigens will trigger on cell receptors the decomposition of
NF-κβ and stimulate the release of pro-inflammatory cytokines,
due to specific gene stimulation
• Hypothesis: TGF-β is responsible for IL-1, TNF-α and NF-κβ
inhibition in the inflammatory cascade.
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Traumeel formula
• Achillea millefolium
• Aconitum napellus
• Arnica montana
• Atropa belladonna
• Bellis perennis
• Calendula officinalis
• Chamomilla recutita
• Echinacea angustifolia
© IAH 2007
• Echinacea purpurea
• Hamamelis virginiana
• Hepar sulfuris
• Hypericum perforatum
• Mercurius solubilis Hahnemanni
• Symphytum officinalis
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The formula of Traumeel consists of 14 components in very subtle dosages,
covering the main symptoms of an inflammation.
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Traumeel formula
Antisuppurative
action
Increase of tone and
stabilization of vasal
permeability, blood
stagnation, venous
stasis
Echinacea ang and
purp., Mercurius sol.
Hahn., Hepar sulfuris
Aconitum, Hamamelis,
Millefolium, Bellis,
Belladonna, Arnica
Inflammation
Stimulation of
circulation
Calendula,
Arnica,
Echinacea purp.,
Symphytum
Analgesic
Aconitum,
Arnica,
Chamomilla,
Hypericum
© IAH 2007
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As seen on this slide there are mainly 4 clinical effects created after the use of
Traumeel. A group of components will intervene at the level of the vasal
permeability and tonus and the venous stasis. Other components create an antisuppurative effect. The third group of components have an analgesic effect and
the last group will stimulate the circulation.
All together, beside the inflammation regulating effect, we see a fast and positive
effect in decreasing the clinical image of inflammation.
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Traumeel galenic forms
• Injections: 1 to 3 times 1 ampule a day in i.m, i.c., s.c., or periarticular
• Drops: 3 times 10 drops a day
• Tablets: 3 times 1 tablet a day (by preference to be solved in the
mouth)
• Ointment: local application 2 times a day, eventually under
bandage
• Gel*: local application 2 times a day
• Drinking ampules*: one ampule a day
* in function of the country
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Worldwide 6 galenic forms are available. The dosage and frequency is mentioned
on the slide per galenic form. Not all forms might be available in every country
worldwide but if available the dosage and frequency remains the same.
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Traumeel: synthesis
• No NSAID but Inflammation Regulating Drug (IRD)
• In inflammations of the locomotorial system and sport injuries
• Arthritis, tendonitis,…
• Distortions, bruises,…
• Traumeel has been shown in vitro to:
• Modulate pro-inflammatory Th-1 and Th-2 cells (TGF-β)1
• Modulate IL-1β, TNF-α and IL-82
• Safe and well tolerated
• Very effective
1. Heine,H.: Immunological Bystander Reaction
2. Porozov S, Cahalon L, Weiser M, Branski D, Lider O, Oberbaum M. Inhibition of IL-1beta and TNF-alpha
Secretion from Resting and Activated Human Immunocytes by the Homeopathic Medication Traumeel S.
Clinical and Develomental Immunology. 2004;11(2):143-149.
© IAH 2007
34
To synthesize we can state that Traumeel is an IRD used in inflammations and
sport injuries. Traumeel has regulating effects over a modulation of inflammation
mediators. It is proven to be a safe and well tolerated medication with a high
effectiveness in the mentioned indications.
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