Interleukin-1β effects on somatostatin release in vitro

Tittle, Angela M. (1998) Interleukin-1β effects on somatostatin release in vitro. Masters thesis, Memorial University of Newfoundland.

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    Available under License - The author retains copyright ownership and moral rights in this thesis. Neither the thesis nor substantial extracts from it may be printed or otherwise reproduced without the author's permission.
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Abstract

Interleukin-1β (an acute phase immune response cytokine) affects central nervous system and hypothalamic control of many neuroendocrine functions. Injections of endotoxins, the cell wall components of gram negative bacteria, have been used experimentally to induce the secretion of interleukin-1β (IL-1β) and other cytokines in mammals. Long term endotoxin treatment in rats causes a decrease in the rate of somatic growth, accompanied by an initial suppression of growth hormone (GH) release parameters (the mass/concentration, peak frequency and baseline levels of secreted GH during a specified time interval) followed by a rebound. The hypothalamic peptide somatostatin (SS) is the primary inhibitor of GH release. IL-1β has been shown to acutely (≤ 30 min) and chronically (> 24 hr) stimulate SS biosynthesis, but no studies have observed IL-1β effects on SS secretion during the intermediate time periods (in hours). The suppression of somatic growth and the initial inhibition of GH release parameters suggests that at some intermediate time point during exposure, endotoxins may adversely regulate somatostatin release through direct mechanisms or via IL-1β mediation. This study used organotypic slice cultures of neonatal rat hypothalamic explants to test the hypothesis that IL-1β induces an inhibition of somatostatin release when cultures are exposed to the cytokine for durations of several hours. This hypothesis may explain how the removal of the negative regulator of GH release would result in the rebound in GH secretion observed in rats treated with endotoxins. In this study, the 2 hr and 12 hr IL-1β incubations resulted in an inhibition of somatostatin release below basal secretion levels. These data indicate that an IL-1β inhibition of SS release may mediate the rebound in GH secretion observed in rats treated chronically with endotoxins. The 24 hr incubation with IL-1β had no significant effect on somatostatin release, suggesting that the chronic effects of IL-1β on growth and GH secretion may be sustained through other hypothalamic mechanisms. This and other data in the literature also suggest that IL-1β plays a complex role in somatostatin regulation having the ability to stimulate (minutes), inhibit (hours) or not alter (days) somatostatin release. -- Certain prostaglandins are known to mediate IL-1β actions. In order to clarify the mechanisms by which IL-1β may inhibit somatostatin secretion, the synthesis of prostaglandin was inhibited. 12 hr incubations of indomethacin alone caused a significant decrease in somatostatin secretion from the cultures derived from the first, and most rostral slices only. Indomethacin combined with IL-1β did not significantly alter somatostatin release compared to basal levels suggesting that in this culture system, under the conditions described, that IL-1β exhibits its effects on somatostatin secretion through a prostaglandin dependent mechanism. Further study will be needed to determine the precise mechanisms and time course by which IL-1β affects somatostatin secretion.

Item Type: Thesis (Masters)
URI: http://research.library.mun.ca/id/eprint/1051
Item ID: 1051
Additional Information: Bibliography: leaves 100-118.
Department(s): Medicine, Faculty of
Date: 1998
Date Type: Submission
Library of Congress Subject Heading: Interleukin-1--Physiological effect; Somatostatin
Medical Subject Heading: Interleukin-1; Somatostatin

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