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42. Kongress der Deutschen Gesellschaft für Rheumatologie, 28. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie, 24. Wissenschaftliche Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie

17.-20. September 2014, Düsseldorf

Inadequately low corticosterone secretion during arthritis is associated with increased IL 1β levels, adrenal dendritic cell accumulation and adrenocortical mitochondria damage

Meeting Abstract

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  • Christine Wolff - Universitätsklinikum Regensburg, Klinik und Poliklinik für Innere Medizin I, Rheumatologie und Klinische Immunologie, Regensburg
  • Katharina Krinner - Universitätsklinikum Regensburg, Klinik und Poliklinik für Innere Medizin I, Rheumatologie und Klinische Immunologie, Regensburg
  • Josef Schröder - Universitätsklinikum Regensburg, Institut für Pathologie, Regensburg
  • Rainer H. Straub - University Hospital Regensburg, Lab. of Exp. Neuroendocrine Immunology and Rheumatology, Dept. of Internal Medicine, Regensburg

Deutsche Gesellschaft für Rheumatologie. Deutsche Gesellschaft für Orthopädische Rheumatologie. Gesellschaft für Kinder- und Jugendrheumatologie. 42. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh); 28. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh); 24. wissenschaftliche Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR). Düsseldorf, 17.-20.09.2014. Düsseldorf: German Medical Science GMS Publishing House; 2014. DocER.26

doi: 10.3205/14dgrh172, urn:nbn:de:0183-14dgrh1721

Veröffentlicht: 12. September 2014

© 2014 Wolff et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Background: In rheumatoid arthritis a functional deterioration of the HPA-axis in form of inadequately low secretion of glucocorticoids in relation to severity of inflammation can be detected. The reasons for this phenomenon are not known. Therefore, this study aimed to find mechanisms responsible for adrenal insufficiency during arthritis.

Methods: To induce arthritis, DA rats were immunized with collagen type II in incomplete Freund adjuvant. Plasma corticosterone, ACTH and cytokines were evaluated by RIA, ELISA or Luminex. ACTH stimulation tests of adrenal glands were done in vitro or by using the ex vivo superfusion method. Adrenal cholesterol was studied by Sudan-III staining, scavenger receptor class BI (SR-BI) and the presence of adrenal immune cells by immunohistochemistry. Fluorescent NBD-cholesterol uptake kinetics were analysed by flow cytometry. Ultrastructural morphology of adrenocortical mitochondria and lipid droplets was studied by electron microscopy.

Results: Initially increased corticosterone and ACTH levels were reduced to baseline levels in the later phase of the disease. Serum levels of corticosterone relative to IL-1β were markedly lower in arthritic than in control animals. IL-1β inhibited ACTH-stimulated corticosterone secretion from adrenocortical cells in vitro. Dendritic cell (DC) density in adrenals was higher in arthritic rats compared to controls but their role is undefined. Cholesterol storage in adrenocortical cells and expression of SR-BI did not differ between groups. However, number of impaired mitochondria largely increased during the course of arthritis, and this was paralleled by reduced numbers of activated cholesterol droplets (inhomogenous droplets relevant for generation of glucocorticoids). In addition, number of normal mitochondria positively correlated with serum corticosterone levels.

Conclusion: In conclusion, DC infiltration into the adrenal gland as well as high levels of IL-1β probably contribute to adrenocortical mitochondrial damage and altered cholesterol breakdown and, consequently, to the adrenal inability to produce adequate amounts of steroid hormones during ongoing arthritis in rats.