These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Immunoneutralization of lipocortin 1 reverses the acute inhibitory effects of dexamethasone on the hypothalamo-pituitary-adrenocortical responses to cytokines in the rat in vitro and in vivo.
    Author: Taylor AD, Loxley HD, Flower RJ, Buckingham JC.
    Journal: Neuroendocrinology; 1995 Jul; 62(1):19-31. PubMed ID: 7566434.
    Abstract:
    Our recent studies suggest that lipocortin 1 (LC1), a potential mediator of the anti-inflammatory, antiproliferative and anti-fever actions of glucocorticoids in peripheral tissues, may also contribute to the powerful negative feedback actions of the steroids on the hypothalamo-pituitary-adrenal (HPA) axis. In the present study we have used (1) an in vitro model to examine the influence of a specific neutralizing monoclonal anti-LC1 antibody (anti-LC1 mAb) on the capacity of dexamethasone to suppress the cytokine-induced release of the 41-amino acid corticotropin-releasing factor (CRF-41) and arginine vasopressin (AVP) from the rat hypothalamus and (2) a passive immunization protocol to assess the contribution of LC1 to the inhibitory actions of dexamethasone on the HPA responses to immunological (i.p. injection of interleukin 1 beta, IL-1 beta) and surgical (laparotomy under ether anaesthesia) stress. In vitro, Il-1 alpha (0.2 ng/ml), IL-1 beta (0.5 ng/ml), IL-6 (10 ng/ml) and IL-8 (1 ng/ml) each caused significant increases in the release of immunoreactive (ir)-CRF-41 and ir-AVP from hypothalami removed from rats adrenalectomized 10-12 days before autopsy; these responses were readily inhibited by preincubation of the tissue with dexamethasone (10(-7) M). The inhibitory actions of the steroid were attenuated and, in many instances, abolished by inclusion in the medium of a monoclonal anti-LC1 antibody (LC1 mAb, diluted 1:15,000); an isotype-matched control antibody (antispectrin alpha+beta, diluted 1:15,000) was ineffective in this regard. IL-1 alpha (0.2 ng/ml), IL-1 beta (0.5 ng/ml) and IL-6 (10 ng/ml) also initiated similar increases in the release of CRF-41 and AVP from hypothalami from intact rats which were effectively blocked by dexamethasone (10(-7) M). However, although the inhibitory actions of the steroid on the pharmacologically evoked release of CRF-41 were specifically overcome by anti-LC1 mAb (diluted 1:15,000), the steroid blockade of AVP release was not. In vivo, rats pretreated with either a polyclonal anti-LC1 antibody (anti-LC1 pAb, 1 ml/day s.c. for 2 days) or a corresponding volume of a nonimmune sheep serum (NSS) responded to immunological (IL-1 beta, 3 micrograms/kg i.p.) or surgical (laparotomy under ether anaesthesia) trauma with significant increases in the serum ACTH and corticosterone concentrations. In the NSS-treated groups, dexamethasone (100 micrograms/kg), which had no effect on the prestress concentrations of ACTH and corticosterone in the blood, completely prevented the HPA responses to both IL-1 beta and laparotomy.(ABSTRACT TRUNCATED AT 400 WORDS)
    [Abstract] [Full Text] [Related] [New Search]