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Chronic stimulation of the hypothalamus-pituitary-adrenal axis in rats by interleukin 1beta: central and peripheral mechanisms.
Cytokine. 1996 Dec; 8(12):910-9.C

Abstract

The authors have studied mechanisms which could be involved in the sustained activation of the hypothalamus-pituitary-adrenal (HPA) axis during continuous infusion of rats with recombinant human interleukin-1beta (IL-1beta). First, the effects of 3 days of intracerebroventricular (i.c.v.) infusion of rats with IL-1 on plasma adrenocorticotropin (ACTH) and corticosterone (B) levels were investigated. Thereafter, changes in plasma ACTH and B levels were followed in rats intraperitoneally (i.p.) infused with IL-1beta after immunoneutralization of corticotropin-releasing hormone (CRH), hypophysectomy (HPX), macrophage depletion using dichloromethylene diphosphonate (Cl2MDP)-containing liposomes, adrenalectomy (ADX) and dexamethasone (DEX) administration, respectively. Infusion of IL-1beta i.c.v., even in doses as low as 0.1 microg/day, induced significant increases in plasma ACTH and B levels. HPX and ADX rats died within 18 h after starting the IL-1beta infusion (0.5 microg/day). Immunoneutralization of CRH significantly decreased and macrophage depletion significantly increased the stimulation of the HPA axis by IL-1 (4.0 microg/day). Administration of high doses of DEX completely abolished the stimulation of the HPA axis by IL-1beta (2.0 microg/day). The present study demonstrates that lower doses of IL-1beta were able to activate the HPA axis when infused i.c.v. compared with i.p. Regarding stimulation of the HPA axis by chronic i.p. infusion of IL-1beta the present study: (1) provides evidence that the CRH system is involved; (2) provides no evidence for a direct stimulatory effect of IL-1beta on the release of B by the adrenal gland which is of sufficient magnitude to resist the stress of chronic i.p. IL-1beta infusion; (3) shows that endogenous macrophage-derived mediators, induced by i.p. IL-1beta infusion, express an overall inhibitory rather than a stimulatory effect on the activity of the HPA axis; (4) demonstrates that exogenous administration of DEX blocks the effect of IL-1beta, which fits well in the concept of an immunoregulatory feedback between IL-1beta and glucocorticoids.

Authors+Show Affiliations

Department of Medicine, University Hospital Nijmegen, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9050749

Citation

van der Meer, M J., et al. "Chronic Stimulation of the Hypothalamus-pituitary-adrenal Axis in Rats By Interleukin 1beta: Central and Peripheral Mechanisms." Cytokine, vol. 8, no. 12, 1996, pp. 910-9.
van der Meer MJ, Sweep CG, Pesman GJ, et al. Chronic stimulation of the hypothalamus-pituitary-adrenal axis in rats by interleukin 1beta: central and peripheral mechanisms. Cytokine. 1996;8(12):910-9.
van der Meer, M. J., Sweep, C. G., Pesman, G. J., Tilders, F. J., & Hermus, A. R. (1996). Chronic stimulation of the hypothalamus-pituitary-adrenal axis in rats by interleukin 1beta: central and peripheral mechanisms. Cytokine, 8(12), 910-9.
van der Meer MJ, et al. Chronic Stimulation of the Hypothalamus-pituitary-adrenal Axis in Rats By Interleukin 1beta: Central and Peripheral Mechanisms. Cytokine. 1996;8(12):910-9. PubMed PMID: 9050749.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Chronic stimulation of the hypothalamus-pituitary-adrenal axis in rats by interleukin 1beta: central and peripheral mechanisms. AU - van der Meer,M J, AU - Sweep,C G, AU - Pesman,G J, AU - Tilders,F J, AU - Hermus,A R, PY - 1996/12/1/pubmed PY - 1996/12/1/medline PY - 1996/12/1/entrez SP - 910 EP - 9 JF - Cytokine JO - Cytokine VL - 8 IS - 12 N2 - The authors have studied mechanisms which could be involved in the sustained activation of the hypothalamus-pituitary-adrenal (HPA) axis during continuous infusion of rats with recombinant human interleukin-1beta (IL-1beta). First, the effects of 3 days of intracerebroventricular (i.c.v.) infusion of rats with IL-1 on plasma adrenocorticotropin (ACTH) and corticosterone (B) levels were investigated. Thereafter, changes in plasma ACTH and B levels were followed in rats intraperitoneally (i.p.) infused with IL-1beta after immunoneutralization of corticotropin-releasing hormone (CRH), hypophysectomy (HPX), macrophage depletion using dichloromethylene diphosphonate (Cl2MDP)-containing liposomes, adrenalectomy (ADX) and dexamethasone (DEX) administration, respectively. Infusion of IL-1beta i.c.v., even in doses as low as 0.1 microg/day, induced significant increases in plasma ACTH and B levels. HPX and ADX rats died within 18 h after starting the IL-1beta infusion (0.5 microg/day). Immunoneutralization of CRH significantly decreased and macrophage depletion significantly increased the stimulation of the HPA axis by IL-1 (4.0 microg/day). Administration of high doses of DEX completely abolished the stimulation of the HPA axis by IL-1beta (2.0 microg/day). The present study demonstrates that lower doses of IL-1beta were able to activate the HPA axis when infused i.c.v. compared with i.p. Regarding stimulation of the HPA axis by chronic i.p. infusion of IL-1beta the present study: (1) provides evidence that the CRH system is involved; (2) provides no evidence for a direct stimulatory effect of IL-1beta on the release of B by the adrenal gland which is of sufficient magnitude to resist the stress of chronic i.p. IL-1beta infusion; (3) shows that endogenous macrophage-derived mediators, induced by i.p. IL-1beta infusion, express an overall inhibitory rather than a stimulatory effect on the activity of the HPA axis; (4) demonstrates that exogenous administration of DEX blocks the effect of IL-1beta, which fits well in the concept of an immunoregulatory feedback between IL-1beta and glucocorticoids. SN - 1043-4666 UR - https://www.unboundmedicine.com/medline/citation/9050749/Chronic_stimulation_of_the_hypothalamus_pituitary_adrenal_axis_in_rats_by_interleukin_1beta:_central_and_peripheral_mechanisms_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1043-4666(96)90122-2 DB - PRIME DP - Unbound Medicine ER -