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European Journal of Integrative Medicine 2 (2010) 71–77
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
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
© 2010 Elsevier GmbH. All rights reserved.
Keywords: NICO; Immune messenger; RANTES; Proinﬂammatory cytokines; Osteonecrosis; Systemic interference
What is NICO (Neuralgia Inducing Cavitational
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: firstname.lastname@example.org (J. Lechner), email@example.com
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 . 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” . 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.
Author's personal copy
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
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
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
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 . 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 .
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 .
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.
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
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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
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 . 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.
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 , 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) .
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
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
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.
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 . 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
Case 2: male patient, age 39
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.
The histological ﬁndings of the NICO area 48/49 show the
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 . 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
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
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 .
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 .
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.
All research done by the authors.
Conﬂict of interest
No conﬂict of interest declared.
 Black GV. A work on special dental pathology. 2nd ed. Chicago: Medico-
Dental Publ. Co.; 1920.
 Fischer MH. Death and dentistry. Springﬁeld, IL: Charles C. Thomas Pub.;
 Bouquot JE, Roberts AM, Person P, Christian J. NICO (neuralgia-
inducing cavitational osteonecrosis): osteomyelitis in 224 jawbone samples
from patients with facial neuralgias. Oral Surg Oral Med Oral Pathol
 Bouquot JE. Neuralgia-inducing cavitational osteonecrosis (NICO). Oral
Surg Oral Med Oral Pathol 1992;73:307–19.
 Bouquot JE, Christian J. Longterm effects of jawbone curettage on the pain
of facial neuralgia. J Oral Maxillofac Surg 1995;53:387–97.
 Lechner J. Störfelder im Trigeminusbereich und Systemerkrankung. VGM
 Bouquot JE, Martin W, Wrobleski G. Computer-based thru-transmission
sonography (CTS) imaging of ischemic osteonecrosis of the jaws—a pre-
liminary investigation of 6 cadaverjaws and 15 pain patients. Oral Surg
Oral Med Oral Pathol Oral Radiol Endod 2001;92:550.
 Bouquot JE, Shankland WE, Margolis II M. Through-transmission alveolar
ultrasonography (TAU)—new technology for evaluation of bone density
and desiccation. Comparison with radiology of 170 biopsied alveolar sites
of osteoporotic and ischemic disease. Oral Surg Oral Med Oral Pathol Oral
Radiol Endod 2002;93.
 Lechner J. Herd, regulation und information. Heidelberg: Hüthig-Verlag;
 Lechner J. Fakt oder Fiktion—Dokumentation des NICO-Störfelds, Reg-
ulationsMedizin 8. Heft 2003;2.
Author's personal copy
J. Lechner, W. Mayer / European Journal of Integrative Medicine 2 (2010) 71–77 77
 Liu C, Papewalis C, Domberg J, Scherbaum WA, Schott M. Chemokines
and autoimmune thyroid diseases. Horm Metab Res 2008;40(June
(6)):361–8 [Epub April 16, 2008].
 Kraaijeveld AO, de Jager SC, de Jager WJ, Prakken BJ, McColl SR, Haspels
I, et al. CC chemokine ligand-5 (CCL5/RANTES) and CC chemokine
ligand-18 (CCL18/PARC) are speciﬁc markers of refractory unstable
angina pectoris and are transiently raised during severe ischemic symptoms.
Circulation 2007;116(October (17)):1931–41 [Epub October 1, 2007].
 Zeremski M, Petrovic LM, Talal AH. The role of chemokines as inﬂam-
matory mediators in chronic hepatitis C virus infection. J Viral Hepat
 Nomura S, Uehata S, Saito S, Osumi K, Ozeki Y, Kimura Y. Enzyme
immunoassay detection of platelet-derived microparticles and RANTES in
acute coronary syndrome. Thromb Haemost 2003;89(March (3)):506–12.
nski R, Olszewski WL, Paluszkiewicz R, Zieniewicz K, Hevelke P,
Zaleska M, et al. Serum cytokine concentration after liver lobe harvesting
for transplantation. Ann Transpl 2002;7(3):36–9.
 Lind M. Growth factor stimulation of bone healing. Effects on
osteoblasts, osteomies, and implants ﬁxation. Acta Orthop Scand Suppl
 Lind M, Deleuran B, Thestrup-Pedersen K, Søballe K, Eriksen EF, Bünger
C. Chemotaxis of human osteoblasts. Effects of osteotropic growth factors.
APMIS 1995;103(February (2)):140–6.
 Robak E, Wo´
zniacka A, Sysa-Jedrzejowska A, Stepie´
n H, Robak T.
Serum levels of angiogenic cytokines in systemic lupus erythemato-
sus and their correlation with disease activity. Eur Cytokine Netw
 Urbaska-Rys H, Wierzbowska A, Robak T. Circulating angiogenic
cytokines in multiple myeloma and related disorders. Eur Cytokine Netw
 Czarkowska-Paczek B, Bartlomiejczyk I, Przybylski J. The serum levels of
growth factors: PDGF, TGF-beta and VEGF are increased after strenuous
physical exercise. J Physiol Pharmacol 2006;57(June (2)):189–97.
 Hirano F, Kobayashi A, Hirano Y, Nomura Y, Fukawa E, Makino
I. Thrombin-induced expression of RANTES mRNA through protease
activated receptor-1 in human synovial ﬁbroblasts. Ann Rheum Dis
 Rathanaswami P,Hachicha M, Sadick M, Schall TJ, McColl SR. Expression
of the cytokine RANTES in human rheumatoid synovial ﬁbroblasts. Dif-
ferential regulation of RANTES and interleukin-8 genes by inﬂammatory
cytokines. J Biol Chem 1993;268(8):5834–9.
 Chicheportiche Y, Chicheportiche R, Sizing I, Thompson J, Benjamin
CB, Ambrose C, et al. Proinﬂammatory activity of TWEAK on human
dermal ﬁbroblasts and synoviocytes: blocking and enhancing effects of
anti-TWEAK monoclonal antibodies. Arthritis Res 2002;4(2):126–33.
 Conlon K, Lloyd A, Chattopadhyay U, Lukacs N, Kunkel S, Schall T, et
al. CD8+ and CD45RA+ human peripheral blood lymphocytes are potent
sources of macrophage inﬂammatory protein 1 alpha, interleukin-8 and
RANTES. Europ J Immunol 1995;25(3):751–6.
 Kimura Y, Pawankar R, Aoki M, Niimi Y, Kawana S. Mast cells and T cells
in Kimura’s disease express increased levels of interleukin-4, interleukin-5,
eotaxin and RANTES. Clin Exp Allergy 2002;32(12):1787–93.
 Staruch MJ, Camacho R, Dumont FJ. Distinctive calcineurin-dependent
(FK506-sensitive) mechanisms regulate the production of the CC
chemokines macrophage inﬂammatory protein (MIP)-1alpha, MIP-1beta,
and RANTES vs IL2 and TNF-alpha by activated human T cells. Cell
 Bolin LM, Murray R, Lukacs NW, Strieter RM, Kunkel SL, Schall TJ, et al.
Primary sensory neurons migrate in response to the chemokine RANTES.
J Neuroimmunol 1998;81(1–2):49–57.
 Karnoub AE, Dash AB, Vo AP, Sullivan A, Brooks MW, Bell GW, et al.
 Immumed, Gesellschaft für angewandte Immunologie, Goethestraße 10,
80336 München, Germany.
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