The role of HPA (hypothalamic-pituitary-adrenocortical) axis in the modulation of inflammatory response by chronic stress in the spleen of mice

The role of HPA (hypothalamic-pituitary-adrenocortical) axis in the modulation of inflammatory response by chronic stress in the spleen of mice

Celkové hodnotenie

Vedecká práca
Prevedenie (dizajn)
Diskusná interakcia
PoužívateľVedecká prácaDizajnDiskusná interakcia
PharmDr. Štefan Husár PhD.60%40%-
Mgr. Alexandra Padová100%100%100%
Ing. Zuzana Brnoliaková PhD.80%60%80%
ISBN: 978-80-972360-4-5

The role of HPA (hypothalamic-pituitary-adrenocortical) axis in the modulation of inflammatory response by chronic stress in the spleen of mice

Ivana Rokytová1 , Alexandra Padová2 , Richard Kvetňanský , Peter Vargovič
1 Institute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Sciences, Dubravska cesta 9/5779, 845 05 Bratislava, Slovakia
2 Institute of Physiology, Faculty of Medicine, Comenius University in Bratislava, Sasinkova 2, 813 72 Bratislava, Slovakia

Chronic or long-term stressors have great impact on health through stress actions on the immune system. Spleen is the largest peripheral immune organ innervated with sympathetic nerves and controlled by adrenomedullary system. However, the mechanism by which chronic stress modulates the inflammatory response evoked by immunogenic stimulus is not sufficiently clarified. Thus, the aim of this study was to elucidate the role of HPA in circumstances of unpredictable chronic stress (UCS) on subsequent inflammatory response evoked by lipopolysaccharide (LPS) in the spleen of mice. 3- months old wild type (WT) as well as corticotrophin-releasing hormone deficient (CRH-/-) males of C57BL/6J  mice were exposed to randomly alternating unpredictable chronic stressors (24 hrs without litter, 2 hrs restraint (in restraint tube), 24 hrs light, 24 hrs cage tilted at 45 °, 2 hrs immobilization (immobilization plate), 2 hrs noise (70-75dB), 5 min forced swimming (37 °C water) for 28 days. Subsequently, 1x 250 µg/kg lipopolysaccharide was administered intraperitoneally. Gene expression was determined by real-time RT-PCR. WT mice exposure to UCS (non-stimulated) showed attenuated expression of inflammatory cytokines (IFNγ, TNFα, IL-6) while elevated anti-inflammatory factor TGFβ1. These changes were accompanied by chronically elevated corticosterone and other glucocorticoid signalization-associated molecules suggesting their anti- inflammatory or immunosuppressive effect. However, prior chronic stress potentiated the inflammatory response to LPS as displayed by increased expression of IFNγ, TNFα, IL-6 and markers of myeloid cells. Since marked corticosterone response to LPS was conserved in UCS animals as well, glucocorticoid signalization molecules showed decreased response suggesting lower sensitivity to glucocorticoids. CRH-/- mice exposure to UCS (non-stimulated) displayed lower expressions of markers of inflammatory myeloid cells (LY6C, LY6G) than WT animals. However, subsequent dose of LPS potentiated response of pro-inflammatory cytokines (IL-6, IL-1β) due to lack of the effect of glucocorticoids while decreased expressions of TNFα and marker of inflammatory monocytes LY6C in comparison with WT mice pointing a role of glucocorticoids in accumulation of inflammatory monocytes in the spleen. Together, our findings show HPA-dependent accumulation of inflammatory monocytes LY6C and expression of TNFα in the spleen. 


Supported by grants VEGA 2/0067/14 and 2/0069/18.



Hello, I have a question which is focused on blood pressure.
It was measure blood pressure in animals in the experiment? If yes, so with what result?

And second question ... I have a similar focused on body weight. You observed differences in experimental groups?

thank you for your question. In our experiment we did not measure blood pressure because for animals it could be as another stressor. It is known, that CRH knockout mice displayed have decreased body weight in comparison with WT mice. However, in UCS group Wild type mice (not CRH-/-) showed lower body weight compared to control group (WT mice). According to our results, 24 hod after chronic stress WT mice showed decreased body weight.