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European Journal of Integrative Medicine 2 (2010) 71–77
Original article
Immune messengers in Neuralgia Inducing Cavitational Osteonecrosis
(NICO) in jaw bone and systemic interference
J. Lechner a,∗, W. Mayer b,1
aGrünwalder Str. 10A, D-81547 München, Germany
bImmumed – Gesellschaft für angewandte Immunologie, Goethestraße 10, D-80336 München, Germany
Received 7 January 2010; received in revised form 24 March 2010; accepted 31 March 2010
Abstract
Aim of the study: In the practice of the author astounding improvements of systemic complaints which accompanied apparently rheumatic, neuralgic
and other chronically inflammatory systemic diseases are consistently observed after cleaning pain free, radiographically normal edentulous areas
of the jaw. These are marked by fatty-degenerative osteonecrosis of the cancellous bone. Thus far, in dental research there are only few scientifically
proven explanations concerning such systemic therapeutic successes.
Methods: In order to clarify systemic interrelations, samples of cancellous bone have been extracted from six subjects. The specimens were then
analyzed by bead-based multiplex technology and tested for 27 immune messengers.
Results: All six specimens concordantly showed highest concentration for IL1-ra (interleukin-1-receptor antagonist) and RANTES. In addition,
in all samples FGFbasic and PDGF-bb have been distinctly evidenced. A statistically high concentration on IL1-RA and RANTES is noticeable
here. The samples’ small distribution and specific concentration on IL1-ra and RANTES, despite the high number of 27 tested mediators, is a
striking figure.
© 2010 Elsevier GmbH. All rights reserved.
Keywords: NICO; Immune messenger; RANTES; Proinflammatory cytokines; Osteonecrosis; Systemic interference
Introduction
What is NICO (Neuralgia Inducing Cavitational
Osteonecrosis)?
Chronic softenings in the jaw are nothing new in medical
history. Already in 1848 textbooks have been published on
fatty dissolution of the jaw bone, which exists separately from
abscesses or acute inflammation of the teeth. In 1915, G.V. Black
– the father of modern dentistry – describes chronic osteitis of
the jaw as a preceding chronic progress which produces cavi-
tations and necrosis of bone cells. Black was impressed by the
expansions of these medical conditions and suggested surgi-
∗Corresponding author. Tel.: +49 89 697 00 55; fax: +49 89 692 58 30.
E-mail addresses: drlechner@aol.com (J. Lechner), wm@immumed.de
(W. Mayer).
URL: http://www.dr-lechner.de (J. Lechner).
1Tel.: +49 89 543 21 77 89; fax: +49 89 543 21 77 82.
cal removal of such “dead appearing” jaw bone [1]. In 1930,
these processes have been specified in the USA for the first time
as “cavitations” and “avascular” (lack of inflammation-induced
vascular proliferations) and less “infectious”. American scien-
tist Dr. Fischer from the University of Cincinnati wrote a book in
1940 titled: “Death and Dentistry” in which he describes chronic
osteitis of the jaw as a “metastasis of microorganisms from these
bone necroses” [2]. Professor G. Bouquot, American pathologist
from University of Pennsylvania gave this cavitation producing
osteonecrosis the name NICO (Neuralgia Inducing Cavitational
Osteonecrosis). In an analysis of more than 200 samples from
patients with trigeminal neuralgia, he noted necrosis of the jaw
bone with concomitant irritation of the trigeminal nerve in all
cases [3–5]. At least 800 medical papers report on NICO. More
than 27 studies concerning osteonecrosis/NICO have been pub-
lished in peer reviewed journals since 1979.
The term NICO suggests, however, that neuralgia is the only
consequence of the osteonecrosis. Possible systemic effects of
this osteolysis of the jaw bone on the organism in terms of
chronic strain are not covered by this nomenclature. Neverthe-
1876-3820/$ – see front matter © 2010 Elsevier GmbH. All rights reserved.
doi:10.1016/j.eujim.2010.03.004
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72 J. Lechner, W. Mayer / European Journal of Integrative Medicine 2 (2010) 71–77
less, we will confine ourselves to the term NICO to describe
these processes in the following. The author published not only
an alleviation of neuralgic complaints of the maxillofacial area,
but also striking improvements of systemic symptoms [6,9]. The
guiding principles of the present analysis are:
•Can immune messengers, cytokines and growth factors gen-
erally be found in tissue samples of NICO sites in the jaw?
•Do immune messenger based inflammatory processes in the
NICO sites exist?
•Which immune messengers appear high in NICO tissue? Can
they possibly be related to systemic diseases?
Problems of radiological diagnosis of NICO
The existence of NICO is largely denied today in main
stream dentistry. The reason is that normal X-ray do not show
the process of bone marrow osteolytic NICO. To answer this
question the author published the following research in sum-
mary [6,9]: healthy parts of the jaw bone (n= 8) and softened
spongial parts (n= 29) were examined in a nuclear absorp-
tion spectrometer to view their mineral contents. The following
mechanisms seem to happen within a NICO regarding the
minerals.
Inside the NICO the hydroxyl apatite of the jaw bone split
with loss of calcium and phosphate. The originally solid bone
structure softens; the clinical image of a rarefying fatty degen-
erate NICO is expected to develop increased permeability for
X-rays and thus a corresponding brightening of the X-ray by
the loss of calcium and phosphate. Spectral analysis shows that,
parallel to the dissolution of the bone, the trace minerals copper,
iron and zinc increase statistically highly significant. Now a fatal
overlapping effect comes up in the NICO area: the increased
tendency to throw a positive radiological picture by loss of
calcium and phosphate is compensated by the increased X-ray-
absorption of accumulation of copper, iron and zinc; this in turn
leads to a balance in the amount of X-ray permeability. The fatal
diagnostic effect: radiological examination of NICO is without
positive results. Thus radiological techniques are not apt for the
exclusive diagnosis of NICO lesions in the jaw bone. The author
documented the extent of this lesions in former publications
[6,9].
Complementary diagnosis of NICO by ultrasound imaging
Obviously low bone density of NICO is difficult to detect
in the maxillofacial bones via radiographic imaging. To give
the practitioner an aid to diagnose the debilitating effects
of bone marrow softening inside NICO lesions a computer-
assisted through-transmission alveolar transmission through
sonography called CAVITAT was developed. CAVITAT pre-
cisely images and identifies cavitational porosity in the jawbone.
To compare radiology with this new ultrasonography technol-
ogy, relative to the ability to identify alveolar bone with NICO
lesions studies show that in 84% of cases the CAVITAT image
changes were more obvious and more readily identified, than
the radiograph for the same site. CAVITAT imaging proved
Fig. 1. Sample of fatty and osteolytic spongial bone of lower jaw.
significantly superior to radiology for the detection of micro-
scopically confirmed osteoporotic and osteopenic NICO bone
[7,8].
Materials and methods
Sampling method of NICO tissue
Following local anesthetics, six subjects underwent intraop-
erative folding back of the gingival flap of the affected part of
the jaw. The overlying cortical bone was removed. All six cases
showed in the spongial area of the jaw bone osteolytic and degen-
erative fatty tissue. This was typical NICO instead of normal jaw
bone. Samples of these osteolytic and fatty-degenerative parts
of cancellous bone were removed. In three subjects, the softened
cancellous bone tissue was extracted from retro molar and third
molar’s areas of the mandible, in cases of the other three from the
corresponding areas of the maxilla. This cancellous bone tissue
could be spooned out in all six cases as fatty-appearing lumps
with a volume up to 1/2 cubic centimeter [10]. The pea-sized
tissue lumps were immediately put into a dry, sterile storage
receptacle (Sarsted Mikro-Tube, Ref. 72.693.005), the screw cap
was sealed airtight und stored at −20 ◦C in the freezer until it
was transported to the laboratory [29].
Macroscopic clinical features of the NICO bone samples
All six samples showed a surprisingly high degree of oste-
olysis of the cancellous bone. The softening is so distinct, that
the marrow space can be sucked and spooned out. Degenera-
tion of the cancellous bone extends in the mandible areas as
far as to the canal of the infraalveolar nerve. Bouquot describes
NICO-induced necrotic, softened cancellous bones as follows:
Hollow cavitations with soft tissue that had undergone fatty
dystrophic changes and demyelination of the bony sheath of
the infraalveolar nerve [3,4]. The six NICO samples present
themselves clinically and macroscopically as fatty lumps of tis-
sue. Fig. 1 shows such a specimen with predominantly fatty
transformation of the jaw bone.
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J. Lechner, W. Mayer / European Journal of Integrative Medicine 2 (2010) 71–77 73
Microscopic features of the NICO bone samples
Every sample was examined histopathologically. The
changes of the bone are similar to those seen in osteoporosis.
The trabeculae are thin with a loss of their bony interconnec-
tions. The widened intertrabecular spaces often contain small
necrotic bone fragments. The fatty marrow shows a mucoid
degeneration with an interstitial edema and an accumulation
of acid mucopolysaccharides staining positively using alcian
blue. These chronic degenerative changes are intermingled with
foci of recent areactive adipocyte necrosis with granular dis-
solution of cytoplasma. The amount of fat cells is constantly
strikingly increased: They show “foamy” changes as sign of
an energetic imbalance of micro-metabolism. Small groups of
foamy makrophagocytic cells are to be seen. Fibrosis is restricted
to small amounts of collagen fibers adjacent to the bony trabec-
ulae. Small nerve fibers are a striking feature in most biopsies of
the jawbone. Nerve fibers are situated in close contact to degen-
erated and necrotic fatty tissue. Typical signs of inflammation,
especially of an inflammatory cell response are missing. There
are no significant leukocyte infiltrates, only few lymphocytes
and mast cells. It is rather the fatty degenerative and osteolytic
aspect, which overweighs. Thus all specimen show degenera-
tive changes of fatty marrow and bone tissue due to insufficient
supply, that is a chronic trophic disorder [30].
Laboratory treatment of the bone samples
After unfreezing, the samples were mixed in the Micro-Tube
with 150 l sterile, phosphate buffered saline (Sigma–Aldrich,
Dulbeccos Phosphate Buffered Saline, Lot. 108K2334), 10 s
vortexed and finally centrifuged (1min, 5000rpm, Eppendorf
5415D). 50 l from the protrusion has been put apart for an
analysis of immune messengers.
Measurement of immune messengers
Determination of human messengers (G-CSF, GM-CSF,
IFN-gamma, IL1beta, IL2, IL4, IL5, IL6, IL7, IL8, IL9,
IL10 IL12(p70), IL13, IL15, IL17, IP10, MCP1, MIP-1alpha,
MIP-1beta,TNF-alpha, Eotaxin, FGFbasic, IL1-ra, PDGF-BB,
RANTES, VEGF) was performed via a bead-based assay
(Bio-Plex Human Group I Cytokine Broad Range Panel, Ref.
171-A11127) on a BioRad Luminex System according to
manufacturer’s instructions. Quantification of the messengers
followed standard curves included in the Bioplex software.
Results
Regarding to immune messengers IL1-ra und RANTES, all
six samples show levels exceeding 800 pg/ml. The interleukin 6
level as well averaged clearly above 1000 pg/ml. However, this
is due to one exceptionally high reading in only one of the six
specimens. In the range from 97 to 298 pg/ml FGFbasic could be
evidenced in all samples, MCP-1 and PDGF-BB were present
at an average concentration above 100pg/ml. The concentration
of messengers IL1b, IL2, IL8, Eotaxin, G-CSF, GM-CSF, IFN-
Fig. 2. Readings of 27-parameter of six NICO samples show high levels in
RANTES (CCL5) and FGFbasic.
gamma, IP10, MIP1b and TNF-alpha averaged in the specimens
at levels between 30 and 90 pg/ml. Messengers IL4, IL5, IL7 and
IL9 were hardly detectable, their average readings lying below
15 pg/ml. IL10, IL12(p70) IL13, IL15, IL17, MIP1a, VEGF
were contained as well in very low concentrations (<15 pg/ml).
Fig. 2 shows the results from the 27-parameter luminex mea-
suring in six processed NICO samples. Readings are in pg/ml,
OOR < below detection limit, OOR>above detection limit with
extrapolated reading.
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74 J. Lechner, W. Mayer / European Journal of Integrative Medicine 2 (2010) 71–77
Discussion of the immunological results
The present research is the first to analyze immune messen-
gers on a broad level within the scope of a screening of processed
samples of degenerated jaw bone tissue (NICO). There is no
study with similar purpose and extensiveness known to the
authors.
Inflammatory and proinflammatory messengers
Primarily striking are the messengers that showed the highest
concentrations, thus IL1-ra and RANTES, as well as FGFba-
sic and PDGF-BB. In this context it stands out, that except of
RANTES, no other proinflammatory messenger, as interferon-
gamma, interleukin 6, interleukin 8 or TNF-alpha, was detected
in such distinctively elevated levels.
RANTES (CCL-5) signifies “regulated on activation nor-
mal T-cell expressed and secreted” and belongs to the
group of chemotactic cytokines with proinflammatory effects.
RANTES affects leukocytes chemotactically, especially T-cells,
eosinophils and basophil granulocytes. Synthesis of RANTES
in circulating T-cells is induced by TNF-alpha and IL1-alpha.
Increased RANTES concentrations in the serum are described
in a large number of inflammatory diseases, e.g. autoimmune
diseases, cardiovascular diseases, chronic infects etc. [11–14].
RANTES levels up to approximately 20 ng/ml in the serum are
regarded as normal [14]. Proceeding on this assumption, the
concentrations of ca. 1 ng/ml metered in the samples have to be
considered as relatively low. However, RANTES “standard lev-
els” for normal jaw bone specimens are not available yet and can
therefore not be evaluated. A systemic proinflammatory effect
seems unlikely, because the RANTES concentration is relatively
low in relation to the serum level.
Anti-inflammatory messengers
In contrast to RANTES, IL1-ra (interleukin-1-receptor antag-
onist) acts strongly anti-inflammatory by blocking signal
transduction at the interleukin-1 receptor, by inhibiting IL2-
secretion and IL2-receptor expression on the cell surface. IL1-ra
can be generated by a variety of cells, e.g. macrophages, mono-
cytes, neutrophils, fibroblasts and ephitelial cells. Due to strong
immunosuppressive effects of IL1-ra, recombinant human IL1-
ra is used successfully by patients with rheumatoid arthritis (e.g.
Kineret®). In regard to IL1-ra, serum concentrations are noted
up to a maximum of 1000 pg/ml in normal subjects [15], com-
pared to that, the concentrations of up to 21,000 pg/ml detected
in the specimens appear as salient. Growth factors FGFbasic
and PDGF-BB are generated, amongst others, by fibroblasts and
stimulate the migration of osteoblasts and the formation of colla-
gen. Both are assigned an important role in osteogenesis [16,17].
FGF concentration in the specimens can be estimated as rela-
tively high, compared to serum concentration of normal subjects
(FGFbasic ca. <2 pg/ml) [18,19]. On the other hand, PDGF-BB
concentration is distinctively below the expected level of normal
subjects (ca. <1.5 ng/ml) [20].
Conclusion
Concluding, it has to be recorded that the present mes-
senger diagram of the analyzed samples, in comparison to
reference levels in serum, accounts for a growth promot-
ing, anti-inflammatory milieu. That is consistent with the lack
of inflammation at the histopathologic analysis [3,4,6]. The
assumption, that the samples high local IL1-ra levels have a sys-
temic effect in terms of an overweight of immunohomoeostatic
processes with a consequent tendency to chronic inflammation,
has to be substantiated in further researches. It is supposed as
immunological fact that any raised immune messenger is a proof
for inflammatory activity. Inflammation is defined not only by
inflammatory and proinflammatory mediators but also by anti-
inflammatory mediators. In spite of the above limitations of this
research NICO can be defined as sort of inflammatory focus.
A determination of messenger levels, in particular those of
IL1-ra, PDGF-BB, FGF and RANTES, in serums of NICO
affected patients would be appropriate to provide indications
of systemic effects of the local NICO messengers. This research
was only targeting NICO as a possible source of immune mes-
sengers, with the striking outcome of high levels of IL1-ra and
RANTES. Naturally the question comes up: How far are the lev-
els of immune messengers in the fatty degenerated NICO probes
to compare with levels in healthy jaw bone? The NICO probes
are by itself altered tissue which has no corresponding structure
in normal bone; similar to pus where a healthy reference is also
not existent.
Salutogenetical aspects of NICO treatment in
complementary medical practice
The reasons for initiating the present study are systemic
phenomena which have been described repeatedly under the key-
words: “osteitis of the jaw” and “maxillary disturbance fields”.
On the one hand, positive therapeutic outcomes of such interfer-
ence field elimination are well known. On the other hand there
are only few verified explanatory models and validated mecha-
nisms referring to the presumed links between systemic diseases
and NICO. Meridian based relations of organs and teeth; orig-
inating from traditional Chinese acupuncture do exist. In this
research the authors’ purpose is to develop an immunologi-
cal based explanatory model of systemic phenomena caused by
NICO jaw surgery.
Case 1: male patient, age 38
Clinical symptoms
Initial complaints: pain in the right knee joint for 12 months.
Previous diagnosis: rheumatic arthritis. Previous medical treat-
ment: prescription of oral Prednisolon and Metotrexat.
Postsurgical findings after NICO treatment
After NICO treatment in the left part of the upper jaw on
September 8th, 2008, the knee pain ceased promptly. In March
2009 the patient gives the following account:
Author's personal copy
J. Lechner, W. Mayer / European Journal of Integrative Medicine 2 (2010) 71–77 75
From February to May 2007,the pain in my knee increased to
such an extent that I went to see my family doctor.He referred
to a rheumatologist.Until the appointment in the mid of Juno
2007,the state of my health worsened,so that I had difficul-
ties to get out of bed in the mornings and down the stairs.My
hands became increasingly stiff as well.The rheumatologist
diagnosed rheumatoid arthritis.The treatment consisted of
medication with Prednisolon and Metrotexat.Because of the
adverse effects I would have had to expect and the statement
of the rheumatologist “I would be able to live a relatively
normal life once adjusted to the medication”,I turned to
complementary medicine.I decided to seek alternative treat-
ment besides orthodox medicine.I contacted Dr.L.in March
2008 to have an examination for disturbance fields in the
head area.In March 2008 you diagnosed NICO lesions in all
four wisdom tooth’s regions.After every operation,four in
total,my condition improved.In the beginning of May 2008 I
stopped the intake of Prednisolon and Metrotexat.Today–in
March 2009 - I’m 95% free of pain,especially when getting
up in the mornings.
Histological findings
The histological diagnosis of the NICO area 28/29 on
September 12th, 2008 showed the following result:
Bone tissue consistently vital with preserved osteocytes.The
marrow spaces show exclusively fat tissue,on the one hand
a very small area with a recent fat tissue necrosis which
shows a lack of adipocyte nuclei,individual,immigrated
neutrophil granulocytes,extravasates of erythrocytes.On
the other hand,areas in where the width of the adipocytes’
caliber is varying,and a foam cellular or fine fibrillar trans-
formed cytoplasm edge.In the remaining marrow spaces,
here a small area with a more recent fat tissue necrosis,
other areas with varying calibers and partly lipoid degener-
ation of the cytoplasm in the way of a trophic dysfunction.
No hemopoietic bone marrow,no relevant inflammation,no
atypias.Presented findings definitely (provided with concur-
rent clinic and radiology)are described as NICO.
Evaluation of pathologic analysis data
The RANTES level of the NICO bone sample of this par-
ticular case of region 28/29, amounting to 911.39 pg/ml, is
considerable increased in the range of the limit of detection.
Where are the connections between local increased RANTES
levels and joints? RANTES is secreted by human fibroblasts
in the synovia and therefore can be part of a progressing
inflammatory process which accompanies rheumatoid arthri-
tis [21,22]. Synoviocytes produce synovia fluid and secrete
effector molecules, which advance inflammations and joint
destruction [23]. They form part of complex network of
autocrine and paracrine factors. A hypothetic causal relationship
regarding the increased RANTES secretion in NICO reads: Cor-
responding individual set-up provided, a permanently increased
level of NICO-RANTES could exert negative impact in terms
of joint inflammation, articular effusions and rheumatoid
arthritis.
Case 2: male patient, age 39
Clinic symptoms
Initial complaints: massive exercise-induced asthma. Pre-
vious diagnosis: exercise-induced asthma of unknown origin.
Previous treatment: cortisone spray, meaning a medically pre-
scribed lifelong intake.
Postsurgical findings after NICO treatment
After NICO treatment in the right part of the lower jaw
in September 2008 regio 48/49, the pain in the knee ceased
promptly. In January 2009, the patient reports:
I wanted to give a short feedback on my previous state of
health and on how I am now.About four years ago,I suddenly
started having problems cycling.On a longer cycling tour
of about 100 km,including many mountain stages,all of a
sudden there was absolutely no power left in my legs.I did not
recover over three months.I went from one doctor to another
and it was declared that I suffered from massive,exercise-
induced asthma.Since then,I had to inhale cortisone spray
every time before I went on a cycling tour.The doctors could
not tell me why I got this asthma,nor where it came from,but
they did tell me that I had to take this spray for the rest of my
life.I had surgery in the jaw bone.Since the treatment of my
teeth,I never had any problems with my maxillary sinus and
I did not need the asthma spray once in the entire summer.I
hope,that it continues like this for the rest of my life.
Histological findings
The histological findings of the NICO area 48/49 show the
following result:
An excised osseous specimen (regio 48/49)with cancellous
bone which shows partially fibrosed,yellow marrow,which is
situated intertrabecular and has increasingly “meandering”,
vital blood vessels and nerve branches.The yellow marrow
shows distinctive,mucoid degeneration.This mucoid degen-
eration suggests a chronic,trophic disorder and belongs to
those findings that are repeatedly seen in the context of NICO.
No inflammatory infiltrates and no atypias.
Evaluation of pathologic analysis data
The RANTES level of the NICO bone sample of this
particular case of area 48/49, amounting to extrapolated
OOR >20,000 pg/ml, is considerably increased above the
range of detection. Where is the connection between local
increased RANTES levels and allergological-pulmonary dis-
orders? RANTES is chemotactic for T-cells, eosinophils and
basophils and takes an active part in mobilizing leucocytes in
inflammatory changed areas. As a result, it is assumed that a gen-
eral cellular activation is taking place, which can often be linked
with diseases like asthma and allergic rhinitis [24,25]. RANTES
is as well a potent activator of the oxidative metabolism, specific
for eosinophils [26]. RANTES activates basophils and thereby
causes the releasing of histamines. A hypothetic causal relation
of the increased secretion of RANTES in the context of NICO
reads: Given a corresponding, individual set-up, a constantly
Author's personal copy
76 J. Lechner, W. Mayer / European Journal of Integrative Medicine 2 (2010) 71–77
increased NICO-RANTES level could exert negative influence
by advancing chronic-inflammatory processes in other parts of
the organism.
Pathogenetic aspects of NICO: approach to a
mediator-based hypothesis of systemic-causal relations
Discussion of systemic relations of the RANTES readings
The issue which gave reason to analyzing the immune mes-
sengers in the six NICO samples had risen from complementary
medical experience of “disturbing fields” in the jaw area. Where
is the explanatory link between local, operative removal of NICO
and the undeniable healing successes in “disturbed fields” of
organic symptoms and clinical presentation? Could it be the
chronically elevated RANTES level from NICO sites in the jaw
bone?
The crucial point of a systemic interpretation of the results
lies in the understanding that NICO is an insidious, chronic sub-
liminal effect. Although RANTES level of all six NICO samples
were noticeably high, they appear rather low in comparison to
RANTES readings which can occur with acute arthritis in serum.
These high serum-levels of RANTES in acute stages should not
be admitted to hide the fact that acute stages of arthritis (case 1)
or asthma (case 2) are actually the late or final stage of a chronic,
asymptomatic promoting phase. Factoring chronicity into the
considerations, increased RANTES level in the local NICO area
lead to the conclusion that the cytokine-regulated signaling in
the body in the course of disturbance field processes is a chronic
challenge for the immune system. The RANTES increase in
NICO can persist for years, is usually clinically unnoticed and
causes a displaced increased development of RANTES level.
Where the local complaints manifest themselves – knee joint
(case 1) or in the bronchial tubes (case 2) depends on genetic
and other individual stress factors. As RANTES is found in many
other systemic diseases it is worth to discuss further aspects of
possible pathogenetic effects of NICO lesions:
RANTES and its role in MS
RANTES has been detected in brain lesions of multiple
sclerosis (MS) patients. IP-10 and RANTES CSF levels were
elevated in MS patients compared with controls. Because both
IP-10 and RANTES are potent T-cell chemoattractants, it is rea-
sonable to postulate that the elevated levels of these chemokines
during active episodes of MS induce accumulation of T-cells
into the CNS. RANTES is a chemo attractant for both T-cells
and macrophages and could be a key proinflammatory factor in
the pathogenesis of MS [27].
RANTES and its role in cancer metastasis
The body’s own stem cells stimulate cancer cells to mutate,
to spread and to form tumors in other organs. A particular sort
of stem cells is required for cancer metastasis. Mesenchymal
stem cells from the bone marrow have been suspected for some
time past. Scientists of Whitehead-Institute Cambridge, Mas.,
USA assume that those stem cells with the aid of messengers
transmute tumor cells into metastasizing cells. These scientists
have already found a molecule which stimulates metastasis:
chemokine CCL5, also called RANTES: The breast cancer cells
stimulate de novo secretion of the chemokine CCL5 (also called
RANTES) from mesenchymal stem cells, which then acts in
a paracrine fashion on the cancer cells to enhance their motil-
ity, invasion and metastasis. This enhanced metastatic ability
is reversible and is dependent on CCL5 signaling through the
chemokine receptor CCR5 [28].
Concluding, the presented hypothetic model of systemic
NICO-impacts can be reduced to a challenge- and stimulation
pattern. There is no direct, monocausal relationship between
disturbance field and disturbance. Interesting, though, is the
author’s longtime clinical experience that in dental therapy prac-
tice a removal of the proinflammatory NICO lesion usually leads
to disappearance of various inflammatory clinical presentations
in our patients.
Authors
All research done by the authors.
Financial support
None.
Conflict of interest
No conflict of interest declared.
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[29] Immumed, Gesellschaft für angewandte Immunologie, Goethestraße 10,
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[30] Gemeinschaftspraxis für Pathologie & Zytologie, Drs. Zwicknagel/Aßmus,
85635 Freising, Germany.
