Lipopolysaccharide Challenge Reveals Hypothalamic-Pituitary-Adrenal Axis Dysfunction in Murine Systemic Lupus Erythematosus

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dc.creatorPham, Grace S.
dc.creatorMathis, Keisa W.
dc.date.accessioned2022-10-14T16:48:29Z
dc.date.available2022-10-14T16:48:29Z
dc.date.issued2018-10-04
dc.description.abstractCrosstalk between the brain and innate immune system may be dysregulated in systemic lupus erythematosus (SLE), a chronic autoimmune disease that presents with dysautonomia and aberrant inflammation. The hypothalamic-pituitary-adrenal (HPA) axis is an endogenous neuro-endocrine-immune pathway that can regulate inflammation following activation of vagal afferents. We hypothesized that chronic inflammatory processes in SLE are in part due to HPA axis dysfunction, at the level of either the afferent vagal-paraventricular nuclei (PVN) interface, the anterior pituitary, and/or at the adrenal glands. To study this, we challenged female control and SLE mice with lipopolysaccharide (LPS) and measured c-Fos expression as an index of neuronal activation, plasma adrenocorticotrophic hormone (ACTH) as an index of anterior pituitary function, and plasma corticosterone as an index of adrenal function. We found that c-Fos expression in the PVN, and plasma ACTH and corticosterone were comparable between unchallenged SLE and control mice. PVN c-Fos was increased similarly in control and SLE mice three hours after LPS challenge; however, there were no changes in plasma ACTH amongst any experimental groups post inflammatory challenge. Plasma corticosterone was markedly increased in LPS-challenged SLE mice compared to their vehicle-treated counterparts, but not in controls. Paradoxically, following LPS challenge, brain and spleen TNF-alpha were elevated in LPS-challenged SLE mice despite heightened plasma corticosterone. This suggests that, despite normal c-Fos expression in the PVN and activation of the HPA axis following LPS challenge, this cumulative response may not adequately defend SLE mice against inflammatory stimuli, leading to abnormally heightened innate immune responses and peripheral inflammation.
dc.description.sponsorshipThis study was partially funded by the American Heart Association (14SDG18320033 to KWM and 16PRE29910012 to GSP), the National Institutes of Health (1K01HL139859 to KWM) and the Lupus Research Alliance (550778 to KWM).
dc.identifier.citationPham, G. S., & Mathis, K. W. (2018). Lipopolysaccharide Challenge Reveals Hypothalamic-Pituitary-Adrenal Axis Dysfunction in Murine Systemic Lupus Erythematosus. Brain sciences, 8(10), 184. https://doi.org/10.3390/brainsci8100184
dc.identifier.issn2076-3425
dc.identifier.issue10
dc.identifier.urihttps://hdl.handle.net/20.500.12503/31873
dc.identifier.volume8
dc.publisherMDPI
dc.relation.urihttps://doi.org/10.3390/brainsci8100184
dc.rights.holder© 2018 by the authors.
dc.rights.licenseAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceBrain Sciences
dc.subjectautoimmune disease
dc.subjectcorticosterone
dc.subjectcytokines
dc.subjectinflammation
dc.subjectneuroimmune
dc.subjectvagus nerve
dc.titleLipopolysaccharide Challenge Reveals Hypothalamic-Pituitary-Adrenal Axis Dysfunction in Murine Systemic Lupus Erythematosus
dc.typeArticle
dc.type.materialtext

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