Time Dependent Mediators of HPA Activation Following Peripheral <i>E. coli</i> Challenge

Time Dependent Mediators of HPA Activation Following Peripheral <i>E. coli</i> Challenge

Bibliographic Details
Main Author: Zimomra, Zachary R.
Language:English
Published: Kent State University / OhioLINK 2012
Subjects:
Neurobiology
Cytokines
PGE
HPA
Online Access:http://rave.ohiolink.edu/etdc/view?acc_num=kent1343074764
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spelling ndltd-OhioLink-oai-etd.ohiolink.edu-kent13430747642021-08-03T05:38:02Z Time Dependent Mediators of HPA Activation Following Peripheral <i>E. coli</i> Challenge Zimomra, Zachary R. Neurobiology Cytokines PGE HPA The hypothalamus-pituitary-adrenal (HPA) axis is activated during an immune challenge to liberate energy and modulate immune responses via feedback and regulatory mechanisms. Inflammatory cytokines and prostaglandins are known contributors to HPA activation, however, most previous studies only looked at specific time-points following lipopolysaccharide (LPS) administration. Since whole bacteria have different immune stimulatory properties compared to LPS, the aim of the current studies was to determine if different immune products contribute to HPA activation at different times following live <i>E.coli</i> challenge. Sprague-Dawley rats were injected intraperitoneally with <i>E.coli</i> (2.5x10<sup>7</sup>CFU) and a time course of circulating corticosterone (CORT), ACTH, inflammatory cytokines, and PGE<sub>2</sub> was developed. Plasma CORT peaked 0.5h after <i>E.coli</i> and steadily returning to baseline by 4h. Plasma PGE<sub>2</sub> correlated with the early rise in plasma CORT, whereas inflammatory cytokines were not detected until 2h. Pretreatment with indomethacin, a non-selective COX inhibitor, completely blocked the early rise in plasma CORT, but not at 2h, whereas pretreatment with IL-6 antibodies had no effect on the early rise in CORT but attenuated CORT at 2h. Interestingly, indomethacin pretreatment did not completely block the early rise in CORT following a higher concentration of <i>E.coli</i> (2.5x10<sup>8</sup>CFU). Further studies revealed that only animals receiving indomethacin prior to <i>E.coli</i> displayed elevated plasma and liver cytokines at early time-points (0.5 & 1h), suggesting prostaglandins suppress early inflammatory cytokine production. Overall, these data indicate prostaglandins largely mediate the early rise in plasma CORT while inflammatory cytokines contribute to maintaining levels of CORT at later time points. 2012-07-26 English text Kent State University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=kent1343074764 http://rave.ohiolink.edu/etdc/view?acc_num=kent1343074764 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
collection NDLTD
language English
sources NDLTD
topic Neurobiology
Cytokines
PGE
HPA
spellingShingle Neurobiology
Cytokines
PGE
HPA
Zimomra, Zachary R.
Time Dependent Mediators of HPA Activation Following Peripheral <i>E. coli</i> Challenge
author Zimomra, Zachary R.
author_facet Zimomra, Zachary R.
author_sort Zimomra, Zachary R.
title Time Dependent Mediators of HPA Activation Following Peripheral <i>E. coli</i> Challenge
title_short Time Dependent Mediators of HPA Activation Following Peripheral <i>E. coli</i> Challenge
title_full Time Dependent Mediators of HPA Activation Following Peripheral <i>E. coli</i> Challenge
title_fullStr Time Dependent Mediators of HPA Activation Following Peripheral <i>E. coli</i> Challenge
title_full_unstemmed Time Dependent Mediators of HPA Activation Following Peripheral <i>E. coli</i> Challenge
title_sort time dependent mediators of hpa activation following peripheral <i>e. coli</i> challenge
publisher Kent State University / OhioLINK
publishDate 2012
url http://rave.ohiolink.edu/etdc/view?acc_num=kent1343074764
work_keys_str_mv AT zimomrazacharyr timedependentmediatorsofhpaactivationfollowingperipheraliecoliichallenge
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