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Inadequate corticosterone levels relative to arthritic inflammation are accompanied by altered mitochondria/cholesterol breakdown in adrenal cortex: a steroid-inhibiting role of IL-1β in rats
  1. Christine Wolff1,
  2. Katharina Krinner1,
  3. Josef A Schroeder2,
  4. Rainer H Straub1
  1. 1Laboratory of Experimental Rheumatology and Neuroendocrino-Immunology, Division of Rheumatology, Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Bavaria, Germany
  2. 2Department of Pathology, University Hospital Regensburg, Regensburg, Bavaria, Germany
  1. Correspondence to Professor Rainer H Straub, Laboratory of Experimental Rheumatology and Neuroendocrino-Immunology, Division of Rheumatology, Department of Internal Medicine I, University Hospital, Regensburg 93042, Germany; rainer.straub{at}klinik.uni-regensburg.de

Abstract

Objectives In rheumatoid arthritis, inadequate cortisol secretion was observed relative to inflammation, but reasons are unknown. Human adrenal glands cannot be investigated due to ethical reasons. Thus, a model of arthritis was studied to test inadequate glucocorticoid secretion and adrenocortical alterations.

Methods Arthritis in DA rats was induced by collagen type II. Plasma hormone (cytokine) levels were determined by ELISA or radioimmunoassay (Luminex). Adrenocortical cells were investigated making use of in vitro culture, immunohistochemistry and imaging techniques, cholesterol uptake studies and electron microscopical morphological analyses of adrenocortical lipid droplets and mitochondria.

Results During the course of arthritis, corticosterone and adrenocorticotropic hormone (ACTH) levels were only elevated on day 1 after immunisation but were in the normal range from day 5 to 55. Serum levels of corticosterone relative to IL-1β were markedly lower in arthritis than in controls. IL-1β inhibited ACTH-stimulated corticosterone secretion from adrenocortical cells in vitro. Cholesterol uptake receptor SR-BI protein was unchanged. Number of altered swollen and cavitated mitochondria increased during the course of arthritis (maximum on day 55), and this was correlated to reduced breakdown of lipid droplets and increased Sudan III-positive lipid accumulation from day 28 to 55. Reduced lipid breakdown measured as a high number of homogenous lipid droplets negatively correlated with plasma corticosterone (p=0.022). Adrenocortical tissue density of normal mitochondria positively correlated with serum corticosterone levels.

Conclusions This study on inadequate adrenal glucocorticoid secretion in arthritis demonstrated altered mitochondria and altered lipid breakdown paralleled by low corticosterone levels in relation to inflammation. IL-1β is a key cytokine.

  • Arthritis
  • Corticosteroids
  • Inflammation

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