Journal of Rehabilitation Medicine 51-11 | Page 45

Inflammatory cytokine levels after post-stroke ELF-EMF
measured in the plasma of post-stroke patients after
ELF-EMF treatment, we found evidence that ELF-
EMF has a substantial impact on interleukins, which
was not noted in the non-ELF-EMF group (Figs 2, 3).
The level of INF-γ was slightly higher, but this increase
was not statistically significant (Fig. 4), and the level
of TGF-β did not change (Fig. 5) after magnetotherapy
treatment.
IFN-γ is considered a key regulator of immune and
inflammatory responses and is absent from normal
brain parenchyma. The data indicate that IFN-γ/IP-10
is a major inflammatory signal pathway in the immune
response to stroke (33). Zhang et al. reported that IFN-γ
can protect the stem cell population during inflamma-
tory response and can stimulate stem cell neurogenesis.
Co-injection of neural stem cells and IFN-γ have been
shown to improve therapeutic outcomes in a model of
ischaemic stroke in rats. IFN-γ treatment significantly
increased neurogenesis in vivo, and induced levels of
subsequent neuronal differentiation of cytokines BDNF,
VEGF, IGF-1 and TGF-β (34).
TGF-β is a multifunctional cytokine that plays an
important role in the control of the immune system,
regulating cell growth, proliferation, differentiation
and apoptosis. TGF-β is also involved in the pathoge-
nesis of cerebrovascular diseases. Evidence suggests
that IFN-γ can modulate TGF-β activity in vitro and
negatively regulate the TGF-β signalling pathway at
wound sites in vivo (29). However, further studies are
needed to assess whether there is crosstalk between
the IFN-γ and TGF-β signalling pathways in various
pathological conditions. In the current study, we ob-
served that the TGF-β plasma level increased in the
non-ELF-EMF group, but was unchanged in the group
exposed to ELF-EMF (Fig. 4). The reported effects
were opposite to those for IFN-γ; however, none of
the changes were statistically significant.
Statistically significant increases in IL-1β (approx-
imately 100%) and IL-2 (approximately 15%) plasma
levels were observed after application of ELF-EMF
treatment (Figs 2 and 3).
IL-2 is generally viewed as a pro-inflammatory cyto-
kine, but its role in acute ischaemic stroke is not clear;
little information is available on IL-2 in post-stroke
patients. It is likely that, as with other pro-inflammatory
cytokines, IL-2 works remarkably in the first phase
after stroke, but its further increase may be destructive.
Nayak et al. found a significant increase in plasma
level of IL-2 in post-stroke patients in the hyperacute
stage (0–24 h), compared with a healthy control group
(35). This level gradually decreased with treatment at
successive intervals: 48, 72, and 144 h in improved
patients, compared to patients who have died. In addi-
tion, IL-2 has been shown to regulate the proliferation
859
and survival of regulatory T cells (Tregs), which exert
important neuroprotective effects in stroke (36).
The current study showed, for the first time, that
ELF-EMF treatment not only increased IL-1β concen-
tration, but also increased IL-1β mRNA expression in
vivo in humans (Fig. 1). This result should be inter-
preted taking into account the complex effects of this
cytokine, and especially its role in acute inflammation
and tissue repair. IL-1β is responsible for a broad spec-
trum of immune and inflammatory responses, induces
T-cell and B-cell activation, and consequently the
synthesis of other pro-inflammatory cytokines (such
as IFN-γ, IL-6 and TNF) and antibody production.
IL-1β is widely considered as a constitutive factor in
the brain; its expression declines to low levels in the
normal adult and increases markedly after injury (37).
It is well documented that ELF-EMF treatment re-
duces the inflammatory response in many pathological
conditions, and thereby improves the condition and
function of a variety of tissues. EMF has also been
shown to modulate an inflammatory cytokine after
traumatic brain injury in rats. Electromagnetic pulse
(EMP) treatment attenuated IL-1β levels up to 10-fold
in cerebrospinal fluid (CSF) within 6 h after initial injury
and also significantly suppressed IL-1β within 17–24 h
after penetrating injury (38). Indeed, some studies have
reported a positive correlation between IL-1β and BDNF
levels, demonstrating that this interleukin is able to mo-
dulate pro-survival BDNF signalling (39). Furthermore,
some cytokines, such as IL-1 and IL-6, are known to
improve neuronal survival in stressed cellular paradigms
(40). The increase in IL-1β expression reported in this
study may be a response to ELF-EMF stimulation and,
in light of the previous research discussed above, it can
be hypothesized that a neuroprotective role of this cyto-
kine might be attributable to IL-1β-dependent regulation
of neurotrophic factors. However, further research is
needed to verify this hypothesis.
ACKNOWLEDGEMENTS
This study was supported by the Department of General Bio-
chemistry, Faculty of Biology and Environmental Protection,
University of Lodz, Lodz, Poland (number 506/1136).
The authors have no conflicts of interest to declare.
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J Rehabil Med 51, 2019