ЗМІНИ ЦИТОКІНОВОГО ПРОФІЛЮ МАКРОФАГІВ, ІНДУКОВАНІ ХРОНІЧНИМ СТРЕСОМ У ІНТАКТНИХ ЩУРІВ ТА ПУХЛИНОНОСІЇВ
Background. The prolonged psychoemotional stress results in the individual adaptive response ensured by the coor- dinated interactions among the nervous, endocrine, and immune systems. A key role in this process is played by the interaction between stress hormones and effector cells of innate immuni...
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Experimental Oncology| _version_ | 1868113233254023168 |
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| author | Voyeykova, I. Fedosova, N. Gogol, S. Chekhun, V. |
| author_facet | Voyeykova, I. Fedosova, N. Gogol, S. Chekhun, V. |
| author_institution_txt_mv | [
{
"author": "I. Voyeykova",
"institution": "R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology of the NAS of Ukraine, Kyiv, Ukraine"
},
{
"author": "N. Fedosova",
"institution": "R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology of the NAS of Ukraine, Kyiv, Ukraine"
},
{
"author": "S. Gogol",
"institution": "R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology of the NAS of Ukraine, Kyiv, Ukraine"
},
{
"author": "V. Chekhun",
"institution": "R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology of the NAS of Ukraine, Kyiv, Ukraine"
}
] |
| author_sort | Voyeykova, I. |
| baseUrl_str | https://exp-oncology.com.ua/index.php/Exp/oai |
| collection | OJS |
| datestamp_date | 2026-06-15T10:40:19Z |
| description | Background. The prolonged psychoemotional stress results in the individual adaptive response ensured by the coor- dinated interactions among the nervous, endocrine, and immune systems. A key role in this process is played by the interaction between stress hormones and effector cells of innate immunity, particularly macrophages (Mph), which con- stitute the first line of host defense. The aim of this study was to experimentally investigate the effects of stress hormones on the cytokine spectrum produced by Mph of the intact and tumor-bearing rats. Materials and Methods. Wistar rats with transplanted Guerin carcinoma were used in a study. to induce experimental chronic stress, animals received dexamethasone or adrenaline (0.5 mg/kg body weight). Plasma levels of tNf-α, IL-6, and IL-10 were determined using ELISA. Results. In the intact animals, prolonged exposure to stress hormones resulted in significant alterations in the macrophage cytokine profile. Adrenaline administration was accompanied by a transient increase in tNf-α (p < 0.05) along with a simultaneous decrease in IL-10 (p < 0.05); subsequently, tNf-α production was suppressed against a marked increase in IL-10 synthesis. Dexamethasone induced an increased tNf-α production at later time points. In rats bearing Guerin carcinoma, the most pronounced changes in tNf-α and IL-10 production were observed following dexamethasone administration: on day 14, tNf-α levels significantly increased, followed by a sharp decline accompa- nied by the elevated IL-10 levels, reflecting Mph polarization from the M1 to the M2 phenotype. This indicates the deve- lopment of immunosuppression and correlates with the active tumor growth. A significant increase in IL-6 production was observed on day 14 under both adrenaline and dexamethasone exposure. Subsequently, adrenaline suppressed IL-6 production, whereas dexamethasone stimulated it, which may indicate the development of glucocorticoid resistance and paradoxical enhancement of inflammation. Conclusion. The prolonged exposure to stress hormones may create condi- tions favorable for tumor progression through suppression of innate immune effectors and development of immunosup- pression, as well as through paradoxical enhancement of inflammatory responses. |
| doi_str_mv | 10.15407/exp-oncology.2026.01.024 |
| first_indexed | 2026-06-15T01:00:28Z |
| format | Article |
| fulltext |
24 ISSN 1812-9269. Experimental Oncology 48 (1). 2026
■
Original Contributions
C i t a t i o n: Voyeykova I, Fedosova N, Gogol S, Chekhun V. Changes in the cytokine profile of macrophages induced by
chronic stress in intact and tumor-bearing rats. Exp Oncol. 2026; 48(1): 24-30. https://doi.org/10.15407/exp-oncolo-
gy.2026.01.024
© PH “Akademperiodyka” of the NAS of Ukraine, 2026. This is an open access article under the CC BY-NC-ND license
(https://creativecommons.org/licenses/by-nc-nd/4.0/)
The relationship between stress and carcinogenesis
has become an increasingly relevant area of re-
search. Stress has been shown to exert a significant
modulatory effect on the functioning of individual
physiological systems as well as the organism as a
whole, increasing not only the risk of malignant
neoplasms but also potentially adversely affecting
treatment outcomes. Prolonged psychoemotional
https://doi.org/10.15407/exp-oncology.2026.01.024
I. Voyeykova *, N. Fedosova, S. Gogol, V. Chekhun
R.E. Kavetsky Institute of Experimental Pathology, Oncology
and Radiobiology of the NAS of Ukraine, Kyiv, Ukraine
* Correspondence: E-mail: voieikova_irina@ukr.net
Changes in Cytokine Profile
of Macrophages Induced by Chronic
Stress in intact and tumor-bearing rats
Background. The prolonged psychoemotional stress results in the individual adaptive response ensured by the coor-
dinated interactions among the nervous, endocrine, and immune systems. A key role in this process is played by the
interaction between stress hormones and effector cells of innate immunity, particularly macrophages (Mph), which con-
stitute the first line of host defense. The aim of this study was to experimentally investigate the effects of stress hormones
on the cytokine spectrum produced by Mph of the intact and tumor-bearing rats. Materials and Methods. Wistar rats
with transplanted Guerin carcinoma were used in a study. To induce experimental chronic stress, animals received
dexamethasone or adrenaline (0.5 mg/kg body weight). Plasma levels of TNF-α, IL-6, and IL-10 were determined using
ELISA. Results. In the intact animals, prolonged exposure to stress hormones resulted in significant alterations in the
macrophage cytokine profile. Adrenaline administration was accompanied by a transient increase in TNF-α (p < 0.05)
along with a simultaneous decrease in IL-10 (p < 0.05); subsequently, TNF-α production was suppressed against
a marked increase in IL-10 synthesis. Dexamethasone induced an increased TNF-α production at later time points. In
rats bearing Guerin carcinoma, the most pronounced changes in TNF-α and IL-10 production were observed following
dexamethasone administration: on day 14, TNF-α levels significantly increased, followed by a sharp decline accompa-
nied by the elevated IL-10 levels, reflecting Mph polarization from the M1 to the M2 phenotype. This indicates the deve
lopment of immunosuppression and correlates with the active tumor growth. A significant increase in IL-6 production
was observed on day 14 under both adrenaline and dexamethasone exposure. Subsequently, adrenaline suppressed IL-6
production, whereas dexamethasone stimulated it, which may indicate the development of glucocorticoid resistance and
paradoxical enhancement of inflammation. Conclusion. The prolonged exposure to stress hormones may create condi-
tions favorable for tumor progression through suppression of innate immune effectors and development of immunosup-
pression, as well as through paradoxical enhancement of inflammatory responses.
Keywords: chronic stress, Guerin carcinoma, macrophages, cytokines.
ISSN 1812-9269. Experimental Oncology 48 (1). 2026 25
Changes in Cytokine Profile of Macrophages Induced by Chronic Stress
stress leads to the formation of an individual adap-
tive response mediated by coordinated interactions
among the nervous, endocrine, and immune sys-
tems. A crucial role in this process is played by the
interactions between stress hormones and effector
cells of innate immunity, particularly macrophages
(Mph), which provide the first line of host defense.
The main mediators of stress are glucocorticoids
and catecholamines. Generally, stress hormones ex-
ert immunosuppressive effects by inhibiting in-
flammatory processes. However, recent studies in-
dicate the existence of more complex mechanisms.
Under prolonged stress exposure, immune cell re-
ceptors may lose sensitivity to regulatory signals,
leading to the paradoxical responses accompanied
by enhanced inflammation and development of
autoimmune disorders [1, 2].
Prolonged exposure to glucocorticoids and cat-
echolamines results in substantial alterations in
Mph functional activity. Stress hormones induce a
shift in macrophage polarization from the proin-
flammatory M1 phenotype to the anti-inflamma-
tory M2 phenotype. This shift is associated with the
suppression of cytotoxic and phagocytic activities
[3—5]. The changes in Mph polarization are ac-
companied by alterations in cytokine production,
characterized by the decreased synthesis of proin-
flammatory cytokines (TNF-α, IL-1β, and IL-6)
and increased production of anti-inflammatory cy-
tokines (IL-10). In certain cases, prolonged cortisol
exposure may lead to glucocorticoid resistance,
characterized by a transition from immunosup-
pression to insensitivity to further hormonal regu-
lation. One mechanism of short-term cortisol-me-
diated anti-inflammatory action involves modula-
tion of the transcription factor NF-κB, which
regulates the expression of proinflammatory cyto-
kines (TNF-α, IL-1, IL-6), chemokines (e.g.,
CXCL8), and adhesion molecules (e.g., ICAM-1).
NF-κB is considered a key mediator of inflamma-
tory responses; its downregulation reduces tran-
scription of proinflammatory genes and suppresses
inflammation. However, prolonged cortisol expo-
sure may reduce Mph receptor sensitivity or recep-
tor density, resulting in the sustained production of
the proinflammatory cytokines despite the elevated
cortisol levels and leading to uncontrolled systemic
inflammation [6—9].
Therefore, chronic stress can modulate immune
responses toward either suppression or uncon-
trolled activation. This becomes particularly criti-
cal in the setting of tumor growth. Macrophages, as
key effectors of antitumor immunity, play signifi-
cant roles in angiogenesis, metastasis, and immu-
nosuppression [10, 11]. In our previous studies, the
prolonged exposure to adrenaline and dexametha-
sone caused profound impairment of the innate
immune effectors, including natural killer cells and
Mph. Initially, a transient activation phase was ob-
served, followed by sustained suppression of activ-
ity. Under prolonged stress hormone exposure,
Mph exhibited M2-like characteristics: decreased
cytotoxic activity, increased arginase activity, and
reduced NO production [12].
Based on these findings, the present study aimed
to investigate experimentally the effects of stress
hormones on the cytokine spectrum produced by
Mph of intact rats and tumor-bearing animals.
Materials and Methods
Animals. The study was carried out on male Wistar
rats, 2.5 months old, weighing 180—200 g, bred at
the vivarium of R.E. Kavetsky Institute of Experi-
mental Pathology, Oncology and Radiobiology of
the National Academy of Sciences of Ukraine
(IEPOR NASU). The animals were kept in the stan-
dard vivarium conditions with natural lighting and
provided with food and water ad libitum. The rats
were handled and kept in accordance with the stan-
dard international rules of biological ethics and the
European Convention for the Protection of Verte-
brate Animals Used for Experimental and Other
Scientific Purposes [13]. The permission to con-
duct research was approved by the Bioethics Com-
mission of the IEPOR NASU (protocol No. 5 dated
06.05.2025). All animals underwent a preliminary
10-day quarantine before being involved in the
study. After the adaptation period, the animals
were weighed and divided into groups.
Tumor strain. Guerin carcinoma cells were ob-
tained from the Bank of Cell Lines from Human
and Animal Tissues of the IEPOR NASU. Tumor
cell transplantation (1 × 106 cells in physiological
solution) was performed subcutaneously in the pel-
vic region of the back.
Agents. Dexamethasone (i/v solution 4 mg/mL,
“Lekhim-Kharkiv”, Ukraine) and adrenaline (i/v
solution 1.82 mg/mL, “Zdorovya”, Ukraine) were
used as stress hormones and administered at a dose
26 ISSN 1812-9269. Experimental Oncology 48 (1). 2026
I. Voyeykova, N. Fedosova, S. Gogol, V. Chekhun
of 0.5 mg/kg of body weight. The agents were ad-
ministered for 12 days, starting from the 2nd day
after the transplantation of Guerin carcinoma, eve
ry other day.
Experimental design. The study included the de-
termination of changes in the production of pro-
and anti-inflammatory cytokines by Mph of the in-
tact and tumor-bearing Wistar rats in the setting of
prolonged exposure to stress hormones. The doses
and schedules of drug administration to intact rats
and animals with tumors were the same.
6 groups were formed: “Intact control, IC” — in-
tact rats injected with physiologic solution (n = 15);
“IC + A” — intact rats injected with adrenaline
(n = 15); “IC + D” — intact rats injected with dexa-
methasone (n = 15); “Tumor growth control,
TGC” — rats with Guerin carcinoma injected with
physiologic solution (n = 15); “Adrenaline” — rats
with tumors injected with adrenaline (n = 15);
“Dexamethasone” — rats with tumors injected with
dexamethasone (n = 15).
The peripheral blood samples from experimen-
tal animals were taken, placed in heparin tubes (In-
terVacTechnology, Estonia), and spun at 1,500 g
for 10 min. Plasma was collected, frozen, and
stored at –20 °C.
The levels of cytokines IL-6, IL-10, and TNF-α
in the peripheral blood plasma were measured on
the 7th, 14th, and 21st days of the experiment.
Assessment of cytokine levels. Cytokine levels in
the blood plasma samples were measured using
commercial test systems Rat TNF-α ELISA Kit; Rat
IL-6 ELISA Kit; and Rat IL-10 ELISA Kit (FineTest,
China) according to the instructions of the manu-
facturer. The immunoenzyme reactions were read
out at λ = 450 nm using an automatic StatFax 2100
reader (USA). The levels of cytokines (pg/mL) in
rat blood plasma were determined using a calibra-
tion curve.
Statistical processing of the results was performed
using the standard methods of variational statistics
with GraphPad Prism 8.0.1 (Graphpad Software
Inc., USA). The significance of the differences be-
tween the groups was assessed using Student’s t-test
and was considered significant at p < 0.05.
Results and Discussion
The administration of adrenaline and dexametha-
sone to the intact rats was associated with changes
in Mph polarization and corresponding altera-
tions in cytokine production. The TNF-α/IL-10
ratio reflects the direction of Mph polarization.
Fig. 1 shows the dynamics of changes in the levels
of the TNF-α/IL-10 ratio in the blood plasma of
intact Wistar rats under prolonged exposure to
stress hormones.
On day 7, adrenaline administration induced a
transient increase in TNF-α levels (19.1 ± 1.8 pg / mL
vs 10.3 ± 1.5 pg / mL in controls, p < 0.05), accompa-
nied by a decrease in IL-10 (289.0 ± 37.3 pg/mL vs
439.7 ± 39.4 pg / mL, p < 0.05). Subsequently, TNF-α
production was suppressed while IL-10 levels sig-
nificantly increased. Dexamethasone stimulated
TNF-α production on day 14 (22.2 ± 4.2 pg / mL vs
10.3 ± 1.5 pg/mL in controls, p < 0.05), whereas
IL‑10 remained at control levels. By day 21, cytokine
profiles in both hormone-treated groups corre-
sponded to the M2 phenotype.
A significant increase in IL-6 levels was observed
on day 14 under both adrenaline (53.3 ± 3.1 pg/mL)
TN
F-
/I
L-
10
ra
tio
IC + A
IC + D
IC
0.06
0.04
0.02
0
7
Days
14 21
Fig. 1. Dynamics of the TNF-α/IL-10 ratio in the blood
plasma of the intact Wistar rats under prolonged exposure
to stress hormones
pg/mL
60
45
30
15
0
7 14
Days
21
IC + A
IC + D
IC
Fig. 2. Dynamics of the IL-6 content in the blood plasma
of intact Wistar rats under prolonged exposure to stress
hormones
ISSN 1812-9269. Experimental Oncology 48 (1). 2026 27
Changes in Cytokine Profile of Macrophages Induced by Chronic Stress
and dexamethasone (61.3 ± 7.5 pg/mL) exposure
compared with controls (22.9 ± 1.4 pg/mL,
p < 0.05). Thereafter, IL-6 levels returned to con-
trol values (Fig. 2).
Thus, data on the production of pro- and an-
ti-inflammatory cytokines by intact rat Mph indi-
cated that prolonged exposure to stress hormones
is accompanied by significant changes in the func-
tional activity of these cells. The observed changes
imply the development of immunosuppression that
could negatively affect the formation of an antitu-
mor immune response.
In rats bearing Guerin carcinoma, similar dy-
namics of TNF-α and IL-10 production were ob-
served, with more pronounced effects following
dexamethasone administration (Fig. 3). On day 14,
TNF-α levels significantly increased; by day 21,
TNF-α levels decreased below those of both intact
controls (2.2-fold) and tumor-bearing controls
(2.1-fold) (p < 0.05), indicating a shift toward M2
polarization and systemic immunosuppression.
The IL-6 production in tumor-bearing rats in-
creased significantly on day 14 following both
adrenaline and dexamethasone administration
(Fig. 4). Subsequently, adrenaline reduced IL-6 to
the TGC group levels, whereas prolonged dexa-
methasone exposure maintained the elevated IL-6
levels. On day 21, the IL-6 levels exceeded those
of intact rats by 1.6-fold, TGC by 3.5-fold, and
adrenaline-treated animals by 2.3-fold (p < 0.05
for all comparisons). Such data most likely indi-
cate a paradoxical increase in the inflammatory
process under the influence of glucocorticoids,
which may result in the development of autoim-
mune diseases or a more profound immunosup-
pressive state.
Notably, dexamethasone-treated animals demon-
strated accelerated tumor growth. Fig. 5 shows
data on the dynamics of growth of Guerin carcino-
ma in experimental rats of different groups. As can
be seen from the presented data, by day 14 of tu-
mor growth, the size of the primary tumor node
was small and nearly identical in rats of all groups
(the mean tumor weight ranged from 0.28 to
0.39 g), which may indicate the preservation of an-
titumor immune responses at this time point. Sub-
sequently, in the TGC and Dexamethasone groups,
a significant acceleration of tumor growth was ob-
served (6.13 ± 1.02 g and 4.67 ± 0.45 g, respective-
ly), coinciding with the marked suppression of
Mph activity and the development of an immuno-
suppressive state.
Thus, prolonged exposure to adrenaline and
dexamethasone led to significant changes in the
functional activity of Mph as one of the main effec-
tors of natural antitumor resistance. However, the
action of these agents differed somewhat. The ac-
tivation of Mph in the intact rats under the influ-
ence of adrenaline occurred at earlier time points:
TN
F-
/IL
-1
0
ra
tio
Adrenaline
Dexamethasone
TGC
IC
0.04
0.03
0.02
0.01
0
7 14
Days
21
Fig. 3. Dynamics of the TNF-α/IL-10 ratio in the blood
plasma of Wistar rats with Guerin carcinoma under pro-
longed exposure to stress hormones
pg/mL
60
45
30
15
14
Days
210 7
Adrenaline
Dexamethasone
TGC
IC
Fig. 4. Dynamics of the IL-6 content in the blood plasma
of Wistar rats with Guerin carcinoma under prolonged
exposure to stress hormones
Tu
m
or
w
ei
gh
t,
g
1
0 7 14
Days
21
3
2
5
6
4
7
Adrenaline
Dexamethasone
TGC
Fig. 5. Dynamics of Guerin carcinoma growth under con-
ditions of modeled chronic stress
28 ISSN 1812-9269. Experimental Oncology 48 (1). 2026
I. Voyeykova, N. Fedosova, S. Gogol, V. Chekhun
already on day 7, a significant increase in TNF-α
production was observed, whereas the significant
activation under dexamethasone was detected on
day 14 of the experiment. This effect may be at-
tributed to the functional characteristics and lo-
calization of the respective hormonal receptors.
Surface membrane adrenergic receptors mediate
a more rapid response than intracellular glucocor-
ticoid receptors, whose activation involves gene
transcription and is therefore slower [14, 15].
At the same time, the most pronounced changes
in TNF-α and IL-10 production in both intact rats
and tumor-bearing animals occurred under dexa-
methasone exposure: on day 14, a significant in-
crease in TNF-α levels was observed, followed by
their sharp decline against a background of rising
IL-10 levels. This pattern reflects the dynamics of
Mph polarization from the pro-inflammatory M1
phenotype toward the anti-inflammatory M2 phe-
notype. Such a process indicates the formation of
immunosuppression, which correlated with active
tumor growth on day 21.
Noteworthy are the changes in the production of
another pro-inflammatory cytokine, IL-6. A signi
ficant increase in IL-6 production in rats with
Guerin carcinoma was observed under the influ-
ence of both adrenaline and dexamethasone on day
14 of the experiment. Subsequently, adrenaline
contributed to the suppression of IL-6 production.
In contrast, prolonged dexamethasone exposure
was accompanied by stimulation of IL-6 produc-
tion: on day 21, the IL-6 levels exceeded those of
intact rats by 1.6-fold, control rats with Guerin car-
cinoma by 3.5-fold, and rats treated with adrena-
line by 2.3-fold (p < 0.05 for all groups). This may
indicate the development of glucocorticoid resis-
tance and paradoxical enhancement of the inflam-
matory process upon glucocorticoid exposure [6—
9]. According to the literature, since IL-6 is a key
activator of the STAT3 signaling pathway, its hyper-
production creates conditions favorable for tumor
progression [16—18], which we also demonstrated
in the Guerin carcinoma model.
In addition, the more pronounced immunomo
dulatory effect of dexamethasone may be associa
ted with the differences in its pharmacodynamic
profile from cortisol and the greater potency in in-
fluencing Mph. In particular, dexamethasone has
a significantly higher affinity for glucocorticoid re-
ceptors than cortisol. On the one hand, this results
in more pronounced suppression of the Mph pro-
duction of pro-inflammatory cytokines (such as
TNF-α, IL-1β, and IL-6) and expression of indu
cible nitric oxide synthase (iNOS), along with the
increased production of anti-inflammatory cyto-
kines (such as TGF-β1, IL-4, and IL-10) and en-
hanced arginase activity [19, 20]. On the other
hand, the higher affinity and binding strength of
dexamethasone to glucocorticoid receptors may
provoke a loss of receptor sensitivity. As a conse-
quence, a paradoxical enhancement of inflamma-
tion may develop even after discontinuation of the
agent, which we observed when assessing IL-6 pro-
duction dynamics in rats with the experimental tu-
mor process.
Thus, the use of adrenaline and dexamethasone
to model chronic stress–induced immunosuppres-
sion has demonstrated that prolonged hormonal
imbalance may create favorable conditions for the
accelerated tumor progression through both the
suppression of the activity of innate immune effec-
tors and the formation of immunosuppression, as
well as the development of a paradoxical inflamma-
tory response.
Acknowledgment
This work was carried out within the framework of
the research project “Development of a Technology
for Identification of Stress-Induced Factors Initia
ting Metastatic Bone Lesions” (State Registration
No. 0125U000655) with the support of the NAS of
Ukraine Target Program “Scientific and Scientific-
Technical (Experimental) Works in the Priority
Area ‘Development of Modern Biological and Bio-
medical Methods, Diagnostic Tools and Technolo-
gies to Support the State during Wartime and Post-
war Periods’ for 2025—2026.”
ISSN 1812-9269. Experimental Oncology 48 (1). 2026 29
Changes in Cytokine Profile of Macrophages Induced by Chronic Stress
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https://doi.org/10.3390/jof7030221
Submitted: January 23, 2026
30 ISSN 1812-9269. Experimental Oncology 48 (1). 2026
I. Voyeykova, N. Fedosova, S. Gogol, V. Chekhun
І. Воєйкова, Н. Федосова, С. Гоголь, В. Чехун
Інститут експериментальної патології, онкології і радіобіології
ім. Р.Є. Кавецького НАН України, Київ, Україна
ЗМІНИ ЦИТОКІНОВОГО ПРОФІЛЮ МАКРОФАГІВ,
ІНДУКОВАНІ ХРОНІЧНИМ СТРЕСОМ
У ІНТАКТНИХ ЩУРІВ ТА ПУХЛИНОНОСІЇВ
Стан питання. Наслідком тривалого психоемоційного навантаження є формування індивідуальної адаптив-
ної реакції, яка забезпечується координованою взаємодією нервової, ендокринної та імунної систем. Ключову
роль у цьому процесі відіграє взаємодія між гормонами стресу та клітинами-ефекторами природної імунної
відповіді (зокрема, макрофагами), які забезпечують першу лінію захисту організму. Мета даної роботи — екс-
периментально дослідити вплив гормонів стресу на спектр цитокінів, продукованих макрофагами інтактних
щурів та тварин з модельним пухлинним процесом. Матеріали та методи. Дослідження проводили на щурах
лінії Wistar; як модель пухлинного росту використана карцинома Герена. Для створення експериментальної
моделі хронічного стресу тваринам вводили дексаметазон або адреналін (0,5 мг/кг ваги). Рівень цитокінів
TNF-α, IL-6 та IL-10 в плазмі периферичної крові щурів визначали за допомогою ELISA. Результати. В ін-
тактних тварин тривалий вплив стресорних гормонів призводив до значних змін спектру цитокінів, проду-
кованих макрофагами. Введення адреналіну супроводжувалося транзиторним підвищенням вмісту TNF-α
(p < 0.05) з одночасним зменшенням вмісту IL-10 (p < 0.05); в подальшому відбувалося пригнічення продукції
TNF-α на тлі суттєвого зростання синтезу IL-10. Дексаметазон обумовлював збільшення продукції TNF-α в
більш пізні терміни. У щурів з карциномою Герена найбільш виражені зміни в продукції TNF-α та IL-10 спо-
стерігали при дії дексаметазону: на 14-ту добу — суттєве збільшення рівнів TNF-α, в подальшому — їх стрімке
зниження на тлі зростання IL-10, що відображає динаміку поляризаційного стану макрофагів від М1 до М2
фенотипу. Такий процес свідчить про формування стану імуносупресії та корелює з активним ростом ново-
утворення. Суттєве зростання рівнів продукції IL-6 відбувалося під впливом адреналіну та дексаметазону
на 14-ту добу експерименту. В подальшому адреналін сприяв пригніченню його продукції, дексаметазон —
її стимулюванню, що може бути ознакою формування стану глюкокортикоїдної резистентності та парадок-
сального посилення запального процесу під впливом глюкокортикоїдів. Висновки. Тривалий вплив гормонів
стресу може створювати сприятливі умови для прискорення пухлинного процесу за рахунок як пригнічення
активності ефекторів неспецифічного імунітету та формування стану імуносупресії, так і формування пара-
доксальної реакції підсилення запального процесу.
Ключові слова: хронічний стрес, карцинома Герена, макрофаги, цитокіни.
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| id | oai:ojs2.ex.aqua-time.com.ua:article-614 |
| institution | Experimental Oncology |
| keywords_txt_mv | keywords |
| language | English |
| last_indexed | 2026-06-16T01:00:10Z |
| publishDate | 2026 |
| publisher | PH Akademperiodyka |
| record_format | ojs |
| resource_txt_mv | exp-oncologycomua/8c/38091f3776b201f835aac06de7a85d8c.pdf |
| spelling | oai:ojs2.ex.aqua-time.com.ua:article-6142026-06-15T10:40:19Z Changes in Cytokine Profile of Macrophages Induced by Chronic Stress in intact and tumor-bearing rats ЗМІНИ ЦИТОКІНОВОГО ПРОФІЛЮ МАКРОФАГІВ, ІНДУКОВАНІ ХРОНІЧНИМ СТРЕСОМ У ІНТАКТНИХ ЩУРІВ ТА ПУХЛИНОНОСІЇВ Voyeykova, I. Fedosova, N. Gogol, S. Chekhun, V. хронічний стрес, карцинома Герена, макрофаги, цитокіни chronic stress, Guerin carcinoma, macrophages, cytokines Background. The prolonged psychoemotional stress results in the individual adaptive response ensured by the coor- dinated interactions among the nervous, endocrine, and immune systems. A key role in this process is played by the interaction between stress hormones and effector cells of innate immunity, particularly macrophages (Mph), which con- stitute the first line of host defense. The aim of this study was to experimentally investigate the effects of stress hormones on the cytokine spectrum produced by Mph of the intact and tumor-bearing rats. Materials and Methods. Wistar rats with transplanted Guerin carcinoma were used in a study. to induce experimental chronic stress, animals received dexamethasone or adrenaline (0.5 mg/kg body weight). Plasma levels of tNf-α, IL-6, and IL-10 were determined using ELISA. Results. In the intact animals, prolonged exposure to stress hormones resulted in significant alterations in the macrophage cytokine profile. Adrenaline administration was accompanied by a transient increase in tNf-α (p &lt; 0.05) along with a simultaneous decrease in IL-10 (p &lt; 0.05); subsequently, tNf-α production was suppressed against a marked increase in IL-10 synthesis. Dexamethasone induced an increased tNf-α production at later time points. In rats bearing Guerin carcinoma, the most pronounced changes in tNf-α and IL-10 production were observed following dexamethasone administration: on day 14, tNf-α levels significantly increased, followed by a sharp decline accompa- nied by the elevated IL-10 levels, reflecting Mph polarization from the M1 to the M2 phenotype. This indicates the deve- lopment of immunosuppression and correlates with the active tumor growth. A significant increase in IL-6 production was observed on day 14 under both adrenaline and dexamethasone exposure. Subsequently, adrenaline suppressed IL-6 production, whereas dexamethasone stimulated it, which may indicate the development of glucocorticoid resistance and paradoxical enhancement of inflammation. Conclusion. The prolonged exposure to stress hormones may create condi- tions favorable for tumor progression through suppression of innate immune effectors and development of immunosup- pression, as well as through paradoxical enhancement of inflammatory responses. Стан питання. Наслідком тривалого психоемоційного навантаження є формування індивідуальної адаптив- ної реакції, яка забезпечується координованою взаємодією нервової, ендокринної та імунної систем. Ключову роль у цьому процесі відіграє взаємодія між гормонами стресу та клітинами-ефекторами природної імунної відповіді (зокрема, макрофагами), які забезпечують першу лінію захисту організму. Мета даної роботи — екс- периментально дослідити вплив гормонів стресу на спектр цитокінів, продукованих макрофагами інтактних щурів та тварин з модельним пухлинним процесом. Матеріали та методи. Дослідження проводили на щурах лінії Wistar; як модель пухлинного росту використана карцинома Герена. Для створення експериментальної моделі хронічного стресу тваринам вводили дексаметазон або адреналін (0,5 мг/кг ваги). Рівень цитокінів tNf-α, IL-6 та IL-10 в плазмі периферичної крові щурів визначали за допомогою ELISA. Результати. В ін- тактних тварин тривалий вплив стресорних гормонів призводив до значних змін спектру цитокінів, проду- кованих макрофагами. Введення адреналіну супроводжувалося транзиторним підвищенням вмісту tNf-α (p &lt; 0.05) з одночасним зменшенням вмісту IL-10 (p &lt; 0.05); в подальшому відбувалося пригнічення продукції tNf-α на тлі суттєвого зростання синтезу IL-10. Дексаметазон обумовлював збільшення продукції tNf-α в більш пізні терміни. У щурів з карциномою Герена найбільш виражені зміни в продукції tNf-α та IL-10 спо- стерігали при дії дексаметазону: на 14-ту добу — суттєве збільшення рівнів tNf-α, в подальшому — їх стрімке зниження на тлі зростання IL-10, що відображає динаміку поляризаційного стану макрофагів від М1 до М2 фенотипу. Такий процес свідчить про формування стану імуносупресії та корелює з активним ростом ново- утворення. Суттєве зростання рівнів продукції IL-6 відбувалося під впливом адреналіну та дексаметазону на 14-ту добу експерименту. В подальшому адреналін сприяв пригніченню його продукції, дексаметазон — її стимулюванню, що може бути ознакою формування стану глюкокортикоїдної резистентності та парадок- сального посилення запального процесу під впливом глюкокортикоїдів. Висновки. Тривалий вплив гормонів стресу може створювати сприятливі умови для прискорення пухлинного процесу за рахунок як пригнічення активності ефекторів неспецифічного імунітету та формування стану імуносупресії, так і формування пара- доксальної реакції підсилення запального процесу. PH Akademperiodyka 2026-06-14 Article Article application/pdf https://exp-oncology.com.ua/index.php/Exp/article/view/614 10.15407/exp-oncology.2026.01.024 Experimental Oncology; Vol. 48 No. 1 (2026): Experimental Oncology; 24-30 Експериментальна онкологія; Том 48 № 1 (2026): Експериментальна онкологія; 24-30 2312-8852 1812-9269 10.15407/exp-oncology.2026.01 en https://exp-oncology.com.ua/index.php/Exp/article/view/614/459 Copyright (c) 2026 Experimental Oncology https://creativecommons.org/licenses/by-nc-nd/4.0/ |
| spellingShingle | хронічний стрес карцинома Герена макрофаги цитокіни Voyeykova, I. Fedosova, N. Gogol, S. Chekhun, V. ЗМІНИ ЦИТОКІНОВОГО ПРОФІЛЮ МАКРОФАГІВ, ІНДУКОВАНІ ХРОНІЧНИМ СТРЕСОМ У ІНТАКТНИХ ЩУРІВ ТА ПУХЛИНОНОСІЇВ |
| title | ЗМІНИ ЦИТОКІНОВОГО ПРОФІЛЮ МАКРОФАГІВ, ІНДУКОВАНІ ХРОНІЧНИМ СТРЕСОМ У ІНТАКТНИХ ЩУРІВ ТА ПУХЛИНОНОСІЇВ |
| title_alt | Changes in Cytokine Profile of Macrophages Induced by Chronic Stress in intact and tumor-bearing rats |
| title_full | ЗМІНИ ЦИТОКІНОВОГО ПРОФІЛЮ МАКРОФАГІВ, ІНДУКОВАНІ ХРОНІЧНИМ СТРЕСОМ У ІНТАКТНИХ ЩУРІВ ТА ПУХЛИНОНОСІЇВ |
| title_fullStr | ЗМІНИ ЦИТОКІНОВОГО ПРОФІЛЮ МАКРОФАГІВ, ІНДУКОВАНІ ХРОНІЧНИМ СТРЕСОМ У ІНТАКТНИХ ЩУРІВ ТА ПУХЛИНОНОСІЇВ |
| title_full_unstemmed | ЗМІНИ ЦИТОКІНОВОГО ПРОФІЛЮ МАКРОФАГІВ, ІНДУКОВАНІ ХРОНІЧНИМ СТРЕСОМ У ІНТАКТНИХ ЩУРІВ ТА ПУХЛИНОНОСІЇВ |
| title_short | ЗМІНИ ЦИТОКІНОВОГО ПРОФІЛЮ МАКРОФАГІВ, ІНДУКОВАНІ ХРОНІЧНИМ СТРЕСОМ У ІНТАКТНИХ ЩУРІВ ТА ПУХЛИНОНОСІЇВ |
| title_sort | зміни цитокінового профілю макрофагів, індуковані хронічним стресом у інтактних щурів та пухлиноносіїв |
| topic | хронічний стрес карцинома Герена макрофаги цитокіни |
| topic_facet | хронічний стрес карцинома Герена макрофаги цитокіни chronic stress Guerin carcinoma macrophages cytokines |
| url | https://exp-oncology.com.ua/index.php/Exp/article/view/614 |
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