Effects of Cytokine Application on Glucocorticoid Secretion in an Animal Model for Systemic Scleroderma

Hans P. Brezinschek, Matthias Gruschwitz, Roswitha Sgonc, Susanne Moormann, Manfred Herold, M. Eric Gershwin, Georg Wick

Research output: Contribution to journalArticle

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Abstract

We previously reported on an altered immune-endocrine feedback loop via the hypothalamo-pituitary-adrenal (HPA) axis in Obese strain (OS) chickens afflicted with spontaneous autoimmune thyroiditis. These animals are deficient in plasma corticosterone increase after antigenic challenge or application of cytokine-containing conditioned medium of mitogen-stimulated spleen cells (CM). To investigate whether the impaired ability to respond to cytokines with glucocorticoid-increasing factor (GIF) activity, e.g. interleukin 1 (IL 1), is restricted to OS chickens as a model for an organ-specific autoimmune disease, we extended our experiments to another autoimmune-prone animal strain, the chickens of the University of California at Davis line 200 (UCD-200). These animals develop an inherited inflammatory fibrotic disease that closely resembles human progressive systemic sclerosis (scleroderma). Application of GIF-containing CM to UCD-200 chickens leads to a transient increase in glucocorticoid serum levels within 1-2 hours comparable to that of controls. But, while corticosterone levels in the latter returned to normal baseline levels after 4 hours, they were still elevated in autoimmune chickens. Although the peak of the glucocorticoid hormone serum concentrations was equal to that of controls, UCD-200 had to secrete twice as much adrenocorticotropic hormone to achieve this corticosterone serum level due to an apparent hyporesponsiveness of the adrenal gland to this secretagoge. The altered cytokine-induced glucocorticoid secretion is found in early as well as in chronic, sclerotic stages of the disease. Cellular alterations in the peripheral blood of UCD-200 chickens during the prolonged elevated corticosterone section, i.e. between 2-4 hours after CM application, are characterized by a significant decrease in the percentage of CD4+ and CD8+ cells. Furthermore, a significant increase in B cells up to 24 hours with a maximum after 1 hour was found. The proliferative response to the mitogen concanavalin A of peripheral mononuclear cells was inversely correlated to the serum corticosterone level, showing a permanent decrease of 80-90% after 1-4 hours in autoimmune animals. This functional alteration in UCD-200 was accompanied by an 80% decrease in serum interleukin 2 (sIL 2) activity 4 hours after CM application. Twenty-four hours later an eight-fold increase in sIL 2 rebound activity was found, indicating that the inhibitory effect of corticosterone in UCD-200 chickens is not long-lasting.

Original languageEnglish (US)
Pages (from-to)719-733
Number of pages15
JournalJournal of Autoimmunity
Volume6
Issue number6
DOIs
StatePublished - Dec 1993

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Systemic Scleroderma
Glucocorticoids
Corticosterone
Chickens
Animal Models
Cytokines
Serum
Mitogens
Interleukin-2
Autoimmune Thyroiditis
Diffuse Scleroderma
Conditioned Culture Medium
Adrenal Glands
Concanavalin A
Interleukin-1
Adrenocorticotropic Hormone
Autoimmune Diseases
B-Lymphocytes
Spleen
Hormones

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Effects of Cytokine Application on Glucocorticoid Secretion in an Animal Model for Systemic Scleroderma. / Brezinschek, Hans P.; Gruschwitz, Matthias; Sgonc, Roswitha; Moormann, Susanne; Herold, Manfred; Gershwin, M. Eric; Wick, Georg.

In: Journal of Autoimmunity, Vol. 6, No. 6, 12.1993, p. 719-733.

Research output: Contribution to journalArticle

Brezinschek, Hans P. ; Gruschwitz, Matthias ; Sgonc, Roswitha ; Moormann, Susanne ; Herold, Manfred ; Gershwin, M. Eric ; Wick, Georg. / Effects of Cytokine Application on Glucocorticoid Secretion in an Animal Model for Systemic Scleroderma. In: Journal of Autoimmunity. 1993 ; Vol. 6, No. 6. pp. 719-733.
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