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Abstract

Cytokines are proteins that interact with cells of the immune system in order to regulate the body's response to disease, infection, inflammation, and trauma. Once induced, cytokines help determine how the immune system should respond and to what degree, and their overproduction or inappropriate production can affect the immune response. Some cytokines act to make disease worse (proinflammatory), whereas others serve to reduce inflammation and promote healing (anti-inflammatory). The effects of Extremely Low Frequency (ELF) 50/60 Hz EMF, produced by many sources, e.g., transmission lines and all devices containing current-carrying wires, including equipment and appliances in industries and in homes, on human health remain unclear. There are many reports that ELF-EMF may modulate the immune response affecting human health. Studies of the possible health effects of EMF has been particularly complex and did not provide straightforward answers. Although the mechanism of this interaction is still obscure it has been shown that ELF-EMF can cause changes in cell proliferation, cell differentiation, cell cycle, apoptosis, DNA replication and expression. The effects of EMF may be useful and harmful depending on the intensity and frequency of the field, the period of exposure and the organism itself. A complete understanding of electromagnetic field effects on organisms helps in curing numerous illnesses as well as protecting from dangerous effects of electromagnetic fields. This review summarizes the effect of EMF exposure on cytokines production, although further studies are required to shed light on the mechanism by EMF regulate immune response influencing cytokines production.
Chapter
EXTREMELY LOW FREQUENCY
ELECTROMAGNETIC FIELD
AND CYTOKINES PRODUCTION
M. Reale and P. Amerio1
Dept of Experimental and Clinical Sciences,
1Dept of Aging Medicine and Science (DMSI), Dermatologic Clinic,
University "G.d'Annunzio" Chieti-Pescara, Chieti, Italy
ABSTRACT
Cytokines are proteins that interact with cells of the immune system
in order to regulate the body's response to disease, infection,
inflammation, and trauma. Once induced, cytokines help determine how
the immune system should respond and to what degree, and their
overproduction or inappropriate production can affect the immune
response. Some cytokines act to make disease worse (proinflammatory),
whereas others serve to reduce inflammation and promote healing (anti-
inflammatory). The effects of Extremely Low Frequency (ELF) 50/60 Hz
EMF, produced by many sources, e.g., transmission lines and all devices
containing current-carrying wires, including equipment and appliances in
industries and in homes, on human health remain unclear. There are many
reports that ELF-EMF may modulate the immune response affecting
human health. Studies of the possible health effects of EMF has been
particularly complex and did not provide straightforward answers.
Although the mechanism of this interaction is still obscure it has been
M. Reale and P. Amerio
2
shown that ELF-EMF can cause changes in cell proliferation, cell
differentiation, cell cycle, apoptosis, DNA replication and expression.
The effects of EMF may be useful and harmful depending on the
intensity and frequency of the field, the period of exposure and the
organism itself. A complete understanding of electromagnetic field
effects on organisms helps in curing numerous illnesses as well as
protecting from dangerous effects of electromagnetic fields. This review
summarizes the effect of EMF exposure on cytokines production,
although further studies are required to shed light on the mechanism by
EMF regulate immune response influencing cytokines production.
INTRODUCTION
As consequence of technological developments and urbanization in the
second half of the 20th century, the magnetic fields generated by electrical
equipment are many times higher than those occurring naturally. The
frequencies of the elettromagnetic fields (EMF) normally encountered by the
population are 50 Hz (in Europe and much of the world) or 60 Hz (in the
United States). Background of 50 Hz magnetic fields generated by electrical
wires and domestic apparels in typical homes vary between 0.01 and 1 mT,
with appliances generating fields of 0.1100 mT [1, 2]. One may differentiate
between occupational and residential sources, and evidences are showed that
these artificial EMF may contribute to a new form of pollution. The EMF
emitted by domestic appliances are generally undetectable at a distance of 1 m,
in fact EMF are directly proportional to the current flowing in the wire and are
very weakly attenuated by the objects they encounter, although they decrease
rapidly in magnitude with distance from the source.
The international agency for the research on cancer (IARC) has classified
EMF as a potential cancinogen in 2001, based on pooled analysis of
epidemiological studies that have demonstrated a small but consistent
correlation between increasing time spent near electro-magnetic generating
sources and certain forms of cancer. Childhood leukemia and hormone
dependent cancers such as breast and prostate cancers appear to be among the
most frequently EMF associate cancers [3-6]. More recently the World Health
organization has claimed that research studies did not support this evidence,
however aknowledged IARC classification. Some concerns remain for people
exposed to EMF and thus is imperative to understand the mechanism of EMF-
tissue interaction. As the immune system is involved in the control of cancer
development and other diseases, many studies have focused on whether or not
Extremely Low Frequency Electromagnetic Field and Cytokines
3
exposure to EMF may affect immunological functions promoting cancer or
disease development. Several studies have examined various immune cell
parameters but with conflicting findings. To further complicate the matter it
seems that different EMF may have different actions on different cells. These
studies have been conducted in vivo and in vitro on different types of cell and
have verified possible potentiation of cancer cell growth [7]. On the other hand
some experimental evidence have found that EMF exposure may be beneficial
such as in prostate cancer inducing cell lines apoptosis [8].
Many other are the biological effects of EMF, researchers have shown that
there are frequencies that applied in controlled ways have beneficial actions to
the body. Thus, pulsed electromagnetic fields in low frequency and intensity
range (Gauss or micro-Tesla) increase oxygenation to the blood, improve
circulation and cell metabolism, improve function, pain and fatigue from
fibromyalgia [9], help patients with treatment-resistant depression [10], and
may reduce symptoms from multiple sclerosis [11]. EMFs has been commonly
used in the field of orthopedics for the treatment of non-union fractures and
failed fusions, taking advange of the evidence that pulsed EMF accelerates the
re-establishment of normal potentials in damaged cells [12] increasing the rate
of healing, reducing swelling and improving the osteogenic phase of the
healing process [13]. Moreover they promote the proliferation and
differentiation of osteoblasts [14]. Long-lasting relief of pelvic pain of
gynaecological origin has been obtained consistently by short exposures of
affected areas to the application of a magnetic induction device producing
short, sharp, magnetic-field pulses of a minimal amplitude [15] and
researchers have shown that EMF improved cell survival after ischemic shock,
and 90% reduced ischemic damage and subsequent disability [16, 17].
Electrophysiological abnormality and cognitive dysfunction associated with
Alzheimer's disease appear reduced with frequency specific pulsed
electromagnetic fields [18]. Due to these effects in the body, EMF have been
used extensively in many other conditions and medical disciplines.
ELECTROMAGNETIC FIELD, HOW DOES IT WORK?
The mechanisms by which EMFs interact with living tissues are currently
unclear. This depending upon by variability in the intensity of EMFs and in the
different exposure durations. It is generally accepted that 50/60 Hz EMF do
not transfer energy to cells in sufficient amounts to directly damage DNA
leading to genotoxic effects. However DNA may function as a Fractal antenna
M. Reale and P. Amerio
4
which confers to it a high reactivity to EMF [19]. Previous studies have
showed that low-frequency EMFs can act at the cellular level and have suggest
that the membrane may be the primary site of interaction with consequently
changes in the intracellular Ca2+ concentration [20-23]. The potentials between
the inner and outer membrane of the living cell within the body, are of about
70 mV. When cells are damaged, these potentials change causing the attraction
of fluids into the interstitial area and swelling or oedema. The application of
pulsed magnetic fields may help the tissues to restore normal potentials at an
accelerated rate, thus aiding the healing of most wounds and reducing swelling
faster. The most effective frequencies found by researchers so far, are very low
frequency pulses of a 50 Hz. These, if gradually increased to 25 pulses per
second for time periods of 600 seconds (10 minutes), condition the damaged
tissue to aid the natural healing process. This EMF conditioning works though
several mechanism including: cellular proliferation and differentiation [24-28],
DNA synthesis [29, 30], RNA transcription [31], protein expression [32],
protein phosphorylation [33], ATP synthesis [34], cell damage and apoptosis
[35-37], micro-vesicle motility [38], inhibition of adherence [39], metabolic
activity [40], hormone production [41], antioxidant enzyme activity [42],
redox-mediated rises in NF-kB [43, 44], tromboxane release [45], CD markers
and cytokines expression [46-48].
CYTOKINES
All cytokines are secreted or membrane-bound small proteins with low
molecular weight, that regulate the growth, differentiation and activation of
immune cells and may act as regulators of responses to infection,
inflammation, and trauma. Their most important functions seem to be local
effects, modulating the behavior of adjacent cells (paracrine) or the cell that
secretes them (autocrine), but in some cases there are significant effects on
distant organs or tissues (endocrine). Despite the fact that most cytokines have
been described and initially named on the basis of a single biological function,
many are multifunctional molecules and their activities include regulating cell
activation, hematopoiesis, apoptosis, cell migration, and cell proliferation. The
effect of an inflammatory response is dictated by the balance between pro- and
anti-inflammatory mediators. Pro-inflammatory cytokines such as interleukin-
1beta (IL-1β), interleukin 6 (IL-6), and Tumor Necrosis Factor α (TNF-α) are
responsible for early responses and amplify inflammatory reactions, whereas
anti-inflammatory cytokines, which include interleukin-4 (IL-4), interleukin-
Extremely Low Frequency Electromagnetic Field and Cytokines
5
10 (IL-10), and interleukin-13 (IL-13), have the opposite effect in that they
limit the inflammatory responses. Any cellular alteration by biological,
phisical or chemical agent provokes changes in local cytokine expression and
release. In these settings, cytokines function to stimulate a host response. The
increasing complexity of pro- and anti-inflammatory cytokine/chemokine
networks has made it crucial to examine them simultaneously and to consider
the loss of their balance as a pathogenetic mechanism in diseases. This is
aimed at controlling the cellular stress and minimizing cellular damage. The
cytokine "controlled" microenvironment in the tissue may also impact several
stages of cancer formation and progression. As the mixture of cytokines that is
present in the tumour microenvironment shapes host immunity, therapeutic
manipulation of the cytokine environment constitutes one strategy to stimulate
protective responses.
Many studies have investigated the EMF effect on release of growth
factors and cytokines [49-51]. Overall, this contribution provide insight into
current areas of debate in the interface between EMF and health and EMF
effect on cytokines related to health or disease, such as on present intriguing
prospects for future therapeutic developments in a variety of disease areas.
MAGNETIC FIELD EXPOSURE AFFECTS CYTOKINES
PRODUCTION WHICH DEPENDS UPON CELL TYPE
The variability of the data on EMF-tissue interaction is great. This effect
is mainly due to the fact that experimental setup and exposure conditions
differed strongly from study to another even if many studies used a 50 Hz
signal. The differences in the findings between these studies can partially be
explained by use of µT signals compared to the milliTesla (mT) ranges. 5 µT
was chose because common daily exposure to EMF will mainly be
experienced in comparable field strengths, ranging from 0.07 µT for average
residential power-frequency magnetic fields in homes in Europe, to about 20
µT under power lines [52]. Studies were designed to look for possible effects
of acute exposure to 50 Hz magnetic fields (10 µT) on the IL-1β, interleukin 2
(IL-2), IL-6, interleukin-1 receptor antagonist (IL-1RA), and the interleukin-2
receptor (IL-2R) production. The effect of continuous and intermittent (1 h
off” and 1 h onwith the field switched on” and off” every 15 s) exposure
to magnetic fields was evaluated in blood samples of young men (2030 years
old). Results showed that exposure to 50 Hz magnetic fields (10 µT)
M. Reale and P. Amerio
6
significantly increases IL-6 when subjects were exposed to an intermittent
magnetic field. However, no effect has been observed on interleukin IL-1β, IL-
2, IL-1RA, and IL-2R [53].
The 7.5 Hz repetitive single pulse waveforms with pulse duration of
300!sec added to osteoblast culture can significantly increased cell count. The
transforming growth factor-β1 (TGF-β1) concentrations in culture medium
after 2-day, 3-day and 4-day were significantly affected by different intensities
of EMF stimulation. These results support findings in the literature suggesting
that EMF treatment may have a stimulatory effect on the osteoblast growth
[54]. Correct frequency and waveform are important [55], but the intensity of
the exposure should also be considered. Li et al. [56] reported that increase of
TNF-α and IL-1β in osteoclast-like cells is related to the intensity of the
electrical field. However, in osteoblasts coltures, EMF irradiation induced an
increase of TGF-β1 release, which was not related to the intensity of the
magnetic field. Results from Gomez-Ochoa et al. [57] indicate that the
application of EMF to the culture of fibroblast-like cells derived from
mononuclear peripheral blood cells does not inhibit the production of
inflammatory cytokines (IL-6 and IL-8), while drastically reduce the
production of cytokines, IL-1β and TNF-α, of macrophagic origin. These data
reveal the inhibition of the production of inflammatory type of cytokines by
activated macrophages, an action that is followed by the increase of IL-10 on
day 21, probably because of the effect of EMF on a residual population of
CD4+ lymphocytes.
Using a magnetic field generated by a pair of circular coils powered by the
generator system, which produced the input voltage of pulse, Ongaro et al.
[58] were able to demonstrate that EMFs significantly modulate the release of
both inflammatory and anti-inflammatory cytokines in human osteoarthritic
synovial fibroblasts (OASFs), with decreased IL-6 production in the presence
of IL-1β, suggesting that cytokine production may be one of the most
important mechanism altered by EMFs in these cells. Interestingly, when
EMFs and an adenosine agonist (Ars) were used in combination these
inhibitory effects were significantly increased with the increase of IL-10
production beeing the most importan effect. The Ongaro's studies showed for
the first time that EMFs can significantly modulate the behavior of human
(OASFs), by inhibiting their inflammatory activities and suggest that the
adenosine pathway is involved in mediating EMF effects, supporting the
conclusion that the EMF-induced increase in adenosine receptor number is
involved in the regulation of at least inflammatory mediators in OASFs. In
Extremely Low Frequency Electromagnetic Field and Cytokines
7
particular, the EMF effects on IL-1β-induced cytokine IL-6, IL-8 and IL-10
production are mainly mediated by the EMF-induced increase in A3 adenosine
receptors. However, as the A3 adenosine antagonist did not completely
abrogate the EMF effect on IL-6, this suggests that EMFs can also act by
different signaling pathways. They have speculated that ‘‘in vivo,’’ the
inhibition of pro-inflammatory pathways, exerted by EMFs and ARs, resulted
in the suppression of the expression of matrix degrading enzymes, thus
contributing to the EMF chondroprotective effects. The authors have
concluded that EMFs display anti-inflammatory effects in human OASFs, by
modulating inflammatory and anti-inflammatory parameters.
Peripheral blood mononuclear cells (PBMCs) have been used frequently
to study effects of EMF on the cell methabolism, inflammatory response since
these are good producer of citokines [59-61].
There are controversies in the literature: some studies show an increase in
IL-1β, IL-2, IL-6 and TNFα, whilst others have shown a decreased production
of these and other cytokines such as IFNγ and IL-10. The exposure of PBMC
to extremely low frequency EMFs with intensity of 2.5 mT, with average time
variation of the order of 1T/s and with induced voltage of about 2 mV,
increased both the spontaneous and the phytohemagglutinin (PHA)- or 12-O-
tetradecanoylphorbol-13-acetate (TPA)-induced production of IL-1 and IL-6
[48]. In another study, Cossarizza et al. [47] suggest that EMFs increase
lymphocyte proliferation by increasing utilization of interleukin-2 (IL-2) and
increasing expression of IL-2 receptor on lymphocyte cell membranes. In fact,
when PBMC were exposed to 50 Hz EMFs for 12 h, the levels of neither IL-
1β, nor IL-2 were increased.
Moreover after 24h of incubation the IL-2 concentration was similar in
EMF-exposed and unexposed PBMC cultures, and only after 48h, in those
cultures which responded to EMF exposure with increased [3H] TdR
incorporation, a marked decrease in IL-2 was observed. Indeed, the
concentration of TNFα decreased significantly immediately after the exposure
period. Other studies showed that in PBMC stimulated with PHA immediately
before the exposure to EMFs the IL-1β, TNFα and IL-2 levels were
significantly higher at the end of the 24 and 48 h EMF exposure, and cells
subjected to three 15-min cycles of EMF, each exposure being followed by
105 min without a field, for a total of 6 hr, released unchanged levels of IL-2,
IFNγ and TNFα during the first 48 hr of incubation respect to unexposed cells.
This indicates that brief exposure to EMF has no significant effect on PBMC.
Unstimulated PBMCs exposed to EMFs with a frequency of 50 Hz and a
M. Reale and P. Amerio
8
potency of 3 mT for 12 h have not significantly increased release of either
IFNγ or IL-6 after 12 and 24 h. In contrast, after PHA challenge, the cells
expressed elevated responses to EMFs exposure, with both the proliferative
responses and the release of cytokines significantly increased [62-64]. In the
study of Jonai et al. [65], trends of greater production of cytokines IL-1β and
IL-2 were noted for PBMCs exposed to 50 Hz EMF at 1 mT, 3 mT to 10 mT
and 30 mT selected as levels seen in the occupational setting. For IL-1β,
though production by samples exposed to 50 Hz was higher for all exposure
levels, statistical significance was detected only for 1 mT and 3 mT exposure
levels. No statistically significant difference in the amount of IL-2 produced
was noted in EMF-exposed cells for all intensities. The same trend of higher
productivity of IL-6 in the EMF-exposed samples was reported at of 1 mT, 3
mT, and 10 mT. No distinct trend of difference in IL-10 production was
detected between EMF-exposed and sham-exposed cells. TNF-α have been
shown to be consistently lower in the cells exposed to magnetic fields at 1 mT,
3 mT, 10 mT and 30 mT.
Some experiments were aimed at investigationg the effect of EMF on
PBMC in in vivo” conditions. Thus, reduced IL-2 and IFN-γ release was
obseved in PHA stimulated PBMC by housewives, exposed for a mean period
of 13 years, in their residences to EMFs (with range 500 KHz-3 GHz) emitted
by radio-television broadcasting (4.3 + 1.4 V/m, while the exposure in the
nearby area was <2.0 V/m.) and reduced PHA-stimulated IFN-γ release from
PBMC from subjects exposed to low frequency EMFs (50 Hz; range 0.2-3.6
microT and 40-120 V/m) in a museum for 20 hours a week showed [66-69].
The same results were showed by a preliminary study that analyzed the IFN-γ
produced by PHA-stimulated PBMC of atopic and non-atopic fertile women
exposed to EMF [70].
Other contrasting results were showed by Ikeda et al. [71] which exposed
PBMCs to three different EMF: linearly polarized (vertical), circularly
polarized, and elliptically polarized, at 50 and 60 Hz. Magnetic flux densities
were set at 500, 100, 20, and 2 microT (rms) for vertical field and at 500
microT (rms) for the rotating fields. He and his collegues showed no effects of
EMFs on the the IFN-γ, TNF-α, IL-2, and IL-10 production of human PBMCs
stimulated with TRL4 and TRL2 ligands after EMF stimulation. To determine
if possible effects of EMF were time dependent, IL-6, IL-1β and TNF-α were
measured at different time points, but early induced cytokine production by
TLR2 and TLR4 stimulation is not influenced by EMF. Induction of IL-10 and
interleukin-8 (IL-8) showed a similar pattern compared to IL-6, IL-1β and
Extremely Low Frequency Electromagnetic Field and Cytokines
9
TNF-α. EMF exposure at t = 2 h reduced IL-10 and exposure at t = 6 h
reduced IL-8 release after TLR2 stimulation with Pam3Cys [72]. Studies on
the kinetic of expression of other cytokines by real time PCR after EMF
exposure indicates the regulation of cell activation via the alternative pathway,
whereas the delayed gene expression of inflammatory cytokines receptor
antagonisnts suggests the suppression of inflammatory processes [73]. Other
more recent results showed that the gene expression of IL-1β, IL-6, IL-8,
TNF-α, IL-12p40, IL-10 in THP-1 monocytic cells, freshly isolated human
monocytes and pharyngeal epithelial cells Detroit 562, were not affected by
EMF exposure [74]. In contrast, we have demonstrated that
immunosuppression is actually the most prominent effect of EMF in human
monocytes and in keratinocytes cell line [75, 76].
MAGNETIC FIELD EFFECTS ON CYTOKINES PRODUCTION
IN ANIMALS
The effects of EMF on animal cytokines production does not differ much
form that of their human counterpart. Murine peritoneal exudate cells (PEC)
exposed to EMF do not alter their IL-1 and IL-6 production [77]. In EMF-
exposed mouse microglial cell line N9, production of TNF-α reached its first
peak at 3 h, gradually decreased, peaked again at 12 h and was then sustained
for up to 24 h after EMF exposure. From 3 to 24 hours of EMF exposure,
expression of TNF-α was significantly induced. Since JAK inhibitor P6 affect
EMF-induced increase of TNF-α expression or protein synthesis Yang et al.
proposed that EMF exposure likely affects microglial activation through the
activation of the JAK-STAT pathway [78]. In a similar way to human studies
also marrow cells harvested from femora and tibiae of 6 week-old mice were
exposed to EMF at different electric field intensities for 2h/day and continued
for 9 days. A statistically significant increase osteoclastogenesis and decrease
bone resorption areas were found. Besides, consistent correlations among
Osteoprotegerin (OPG), receptor activator of nuclear factor-kappaB ligand
(RANKL), Macrophage colony-stimulating factor (M-CSF), osteoclast
numbers, and bone resorption after exposure to different intensities of EMF
were observed by Chang et al. [79], demonstrating that EMF with different
intensities could regulate osteoclastogenesis, bone resorption, OPG, RANKL,
and M-CSF concentrations in marrow culture system.
M. Reale and P. Amerio
10
When gene expression of inflammatory cytokines was analyzed in spleen
of Sprague Dawley rats with inflammation of the Achilles' tendon, 24 hours
after 4 hours application of EMF no effect on cytokine expression was
observed [80]. In order to investigate the effects of acute and subchronic
exposure of whole body mice to 50Hz EMF, Ushiyama and Ohkubo [81, 82]
measured the behavior of intra-microvascular leukocytes in the cutaneous
microcirculation and the IL-1β and TNF-α concentration. The magnetic flux
densities used for the acute exposure (30 minutes) were controlled at 3, 10, 30
mT, while for subchronic exposure study mice were exposed to 50 Hz EMF at
0.3, 1.0 and 3.0 mT. The 50Hz EMF exposure was intermittently performed
everyday for 20 hours/day for 15 days. No noticeable changes in plasma IL-1β
and TNF-a concentration, measured by ELISA, were observed. Thus, the
authors hypothesize that 50 Hz EMF increased interaction between leukocyte
and endothelial cell but not change IL-1β and TNF-α levels. Reduction of IL-2
receptor expression and changes in blood lymphocyte subsets were observed
in Baboons exposed for six weeks to 60 Hz EMF [83].
As to underline that the effect of EMF may depend upon the type of the
field used and upon the type of wave shape, when rats were exposed during 3
or 6 days (8 minute a day) to an ELF magnetic field of a complex shape
generated by a device used in medicine and two different RMS values of
magnetic field induction (0,06mT and 0,14mT) were applied during the
experiment, the concentration of TNF-a in serum of rats increased [84].
Indeed, magnetic field strength and age of the animals may be important
variables in determining whether EMF exposure will affect inflammatory
cytokines activity. Young animals were more susceptible than older animals to
the effects of EMF on IL-1 activity. A significant reduction in IL-1 activity in
ewe lambs exposed for 3 ± 4 months to a mean magnetic and electric field of
3.5 mT and 5.8 kV/m exposure was observed. No significant differences were
found for IL-1 or IL-2 activity in sheep exposed for long-term to EMF from a
500kV transmission line [85].
MAGNETIC FIELD, CYTOKINES AND DISEASE
Many are the possible fields of application of EMF in medicine.
Laboratory research indicated that EMF may prevent bone loss through
promoting TGF-β1 and inhibiting IL-6 secretion [86, 87], promoting tissue
regeneration [88], and signaling osteogenic differentiation and mineralization
Extremely Low Frequency Electromagnetic Field and Cytokines
11
[89]. Since EMFs display anti-inflammatory effects in human OASFs, by
modulating inflammatory and anti-inflammatory parameters, Ongaro et al.
[58] have speculate that in vivo the inhibition of pro-inflammatory pathways,
exerted by EMFs, may finally result in the suppression of the expression of
matrix degrading enzymes, thus contributing to the EMF chondroprotective
effects in osteoarthritis patients. Human PBMCs obtained from subjects with
early Rheumatoid arthritis (RA) were exposed for 15 and 30 minutes to the 20
Hz EMF and cultured for 48 hrs. A decrease of TNF-α release in exposed cells
was observed, with a more evident effect in cells stimulated with LPS, but no
significant difference was appreciable between the two different times, i.e. 15
and 30 minutes, of exposure. The TNF-RII expression was decreased in
exposed cells. Take in account the role of TNFα and TNF-R in RA, these
results reinforce the concept that magneto-therapy can be considered as a
complementary therapy for RA [90].
In addition to its effect on orthopedics, EMF has also been reported to
have a similar effect in tissue regeneration such as in accelerating wound
healing for both animal and human [91, 92], regenerate nerve tissue [93],
helping to reduce post operational pain, chronic musculoskeletal pain and pain
from carpal tunnel syndrome [94]. The possible mechanisms for tissue
regeneration and pain management has been suggested. It has been postulated
that a decrease in the production of inflammatory-type cytokines (IL-1β and
TNF-α) and an IL-10 increase may mediate the mechanims of tissue
regenation expecially in chronic wounds. EMF produced a decrease in mean
pain scores, in patients undergoing breast reduction for symptomatic
macromastia, with a concomitant reduction of IL-1β concentration in the
wound exudates while no significant differences were found for TNF-α,
VEGF, and FGF-2 concentrations [49, 57].
CONCLUSION
The mechanism proper of the favorable action of the pulsed magnetic field
on the living organism is not quite clear so far, clinical investigations revealed,
however, a favorable anti-inflammatory, anti-angioedematous and analgesic
therapeutic effect. Thus, EMF has potential to become an effective therapy for
MS, fibromyalgia, chronic fatigue, arthritis and many other chronic conditions
by modulation of cytokines production that affect tissue regeneration, pain
relief, anti-inflammation and anti-microbial response. The optimal frequency
M. Reale and P. Amerio
12
of the magnetic field and duration of exposition time must be selected with
regard to the character of the disease. The value of pulsed electromagnetic
field therapy has been shown to cover a wide range of conditions, with well
documented trials carried out by hospitals, rheumatologists and
physiotherapists. The European Union accepted the use of EMF therapy in
many areas including healing and recovery from trauma, degeneration and the
treatment of the pain associated with these condition. USA’s FDA approved
EMF therapy to stimulate bone repair in non-union and other fractures. Israel
accepted the use of EMF therapy for migraine headaches and Canada for
powered muscle stimulator. The advantage of this therapeutic method is the
non-contact, non-invasive, non-pharmacological and minimal number of
contraindications.
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P. K.
... The ELF-EMF frequencies found in the normal living and working situations are 50 Hz in Europe and parts of the world, and 60 Hz in US. The intensity of the magnetic fields that are generated by domestic conduits and wiring vary between 0.01 and 1 millitesla (mT) (Reale and Amerio, 2013). Appliances generate fields of 0.1-100 mT (Renew and Swanson 1994;Reale and Amerio 2013). ...
... The intensity of the magnetic fields that are generated by domestic conduits and wiring vary between 0.01 and 1 millitesla (mT) (Reale and Amerio, 2013). Appliances generate fields of 0.1-100 mT (Renew and Swanson 1994;Reale and Amerio 2013). This data, although several decades old, is still valid since most buildings are still using older versions of wiring and appliances that were designed and used when the buildings were built. ...
... All in all, the correct frequency and waveform are important, but they are not the only factors for the effects. The intensity of the exposure, the age of the recipient, and diet affect the immune system and, consequently, biological susceptibility (Reale and Amerio 2013). Some of the examples of possible positive biological effects, either harmful or therapeutic, are listed below: ...
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A(3) adenosine receptors (ARs) play a pivotal role in the development of cancer and their activation is involved in the inhibition of tumor growth. The effects of pulsed electromagnetic fields (PEMFs) on cancer have been controversially discussed and the detailed mechanisms are not yet fully understood. In the past we have demonstrated that PEMFs increased A(2A) and A(3)AR density and functionality in human neutrophils, human and bovine synoviocytes, and bovine chondrocytes. In the same cells, PEMF exposure increased the anti-inflammatory effect mediated by A(2A) and/or A(3)ARs. The primary aim of the present study was to evaluate if PEMF exposure potentiated the anti-tumor effect of A(3)ARs in PC12 rat adrenal pheochromocytoma and U87MG human glioblastoma cell lines in comparison with rat cortical neurons. Saturation binding assays and mRNA analysis revealed that PEMF exposure up-regulated A(2A) and A(3)ARs that are well coupled to adenylate cyclase activity and cAMP production. The activation of A(2A) and A(3)ARs resulted in the decrease of nuclear factor-kappa B (NF-kB) levels in tumor cells, whilst only A(3)ARs are involved in the increase of p53 expression. A(3)AR stimulation mediated an inhibition of tumor cell proliferation evaluated by thymidine incorporation. An increase of cytotoxicity by lactate dehydrogenase (LDH) release and apoptosis by caspase-3 activation in PC12 and U87MG cells, but not in cortical neurons, was observed following A(3)AR activation. The effect of the A(3)AR agonist in tumor cells was enhanced in the presence of PEMFs and blocked by using a well-known selective antagonist. Together these results demonstrated that PEMF exposure significantly increases the anti-tumor effect modulated by A(3)ARs.
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The eventuality of adverse effects due to exposure to extremely low frequency (ELF) magnetic field under discussion among both researchers and proctectionists. It is important to understand if some functions of the immune system may be affected by the exposure to ELF magnetic fields. We have studied the tumor necrosis factor α (TNF α) and interferon γ (IFN γ) production by human peripheral blood mononuclear cells (PBMC) exposed in vitro to sinusoidal 50 Hz magnetic fields after stimulation by means of different inducers. Employing an enzyme-linked immunosorbent assay (ELISA), we have not found effects on IFN γ production, while a decrease in TNF α production by exposed cells is observed in different experimental conditions.
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