Abstract
BackgroundBasic and clinical studies suggest that hypothalamic-pituitary-adrenal (HPA) axis is the neuroendocrine-immnue pathway that functionally regulates the chronic inflammatory disease including asthma. Our previous studies showed corresponding changes of cytokines and leukotriene B4 (LTB4) between brain and lung tissues in antigen-challenged asthmatic rats. Here, we investigated how the increased LTB4 level in brain interacts with HPA axis in regulating antigen-induced asthmatic response in sensitized rats.MethodsOvalbumin-sensitized rats were challenged by inhalation of antigen. Rats received vehicle, LTB4 or U75302 (a selective LTB4 BLT1 receptor inhibitor) was given via intracerebroventricular injection (i.c.v) 30 min before challenge. Lung resistance (RL) and dynamic lung compliance (Cdyn) were measured before and after antigen challenge. Inflammatory response in lung tissue was assessed 24 h after challenge. Expression of CRH mRNA and protein in hypothalamus were evaluated by RT-PCR and Western Blot, and plasma levels of adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were measured using the ELISA kits.ResultsAntigen challenge decreased pulmonary function and induced airway inflammation, evoked HPA axis response in sensitized rats. Administration of LTB4 via i.c.v markedly attenuated airway contraction and inflammation. Meanwhile, LTB4 via i.c.v markedly increased CORT and ACTH level in plasma before antigen challenge, and followed by further increases in CORT and ACTH levels in plasma after antigen challenge in sensitized rats. Expression of CRH mRNA and protein in hypothalamus were also significantly increased by LTB4 via i.c.v in sensitized rats after antigen challenge. These effect were completely blocked by pre-treatment with BLT1 receptor antagonist U75302 (10 ng), but not by BLT2 antagonist LY255283.ConclusionsLTB4 administered via i.c.v down-regulates the airway contraction response and inflammation through activation of the HPA axis via its BLT1 receptor. This study expands our concept of the regulatory role of intracranial inflammatory mediators in inflammatory diseases including asthma. The favourable effects of LTB4 on the HPA axis may help to explain the phenomenon of self-relief after an asthmatic attack.
Highlights
Basic and clinical studies suggest that hypothalamic-pituitary-adrenal (HPA) axis is the neuroendocrineimmnue pathway that functionally regulates the chronic inflammatory disease including asthma
We found that the changes of Th1/Th2 paradigm [10], and the content of leukotriene B4 (LTB4) in the cerebral cortex increases corresponding to their changes in bronchoalveolar lavage fluid (BALF) or lung tissue in inflammatory status of asthmatic rats [11]
Airway inflammation To further study the effect of LTB4 i.c.v on antigeninduced airway inflammation, we evaluated the inflammatory cell infiltration in OVA sensitized rats. 24 h after the final OVA challenge, inflammatory cells including polymorphonuclear (PMN) cells and monocytes in BALF were counted
Summary
Basic and clinical studies suggest that hypothalamic-pituitary-adrenal (HPA) axis is the neuroendocrineimmnue pathway that functionally regulates the chronic inflammatory disease including asthma. The adaptive responses could be impaired by some physical and psychological stressors in neuroendocrine-immune feedback system The hypothalamic-pituitary-adrenal (HPA) axis is the major pathway in NEI, hypothalamus secretes corticotropin releasing hormone (CRH) when the HPA axis is activated. This molecule travels to the anterior pituitary gland, which responds to its presence by secreting a pulse of adrenocorticotropin hormone (ACTH). The ACTH signal is carried through the peripheral circulation to the adrenal glands, which synthesize and release cortisol and lead to reduction of inflammation
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
