Medizinische Universität Graz - Research portal
Selected Publication:
Brezinschek, HP; Gruschwitz, M; Sgonc, R; Moormann, S; Herold, M; Gershwin, ME; Wick, G.
Effects of cytokine application on glucocorticoid secretion in an animal model for systemic scleroderma.
J Autoimmun. 1993; 6(6):719-733
Doi: 10.1006/jaut.1993.1060
Web of Science
PubMed
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- Leading authors Med Uni Graz
- Brezinsek Hans-Peter
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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 secretagogue. 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Adrenocorticotropic Hormone - pharmacology
- Animals - pharmacology
- Autoimmune Diseases - genetics
- Biological Factors - pharmacology
- Biological Response Modifiers - pharmacology
- Cells, Cultured - pharmacology
- Chickens - genetics
- Concanavalin A - pharmacology
- Connective Tissue Diseases - genetics
- Corticosterone - deficiency
- Culture Media, Conditioned - pharmacology
- Disease Models, Animal - pharmacology
- Feedback - pharmacology
- Fibrosis - pharmacology
- Interleukin-2 - biosynthesis
- Leukocyte Count - biosynthesis
- Lymphocyte Activation - drug effects
- Lymphocyte Subsets - drug effects
- Pituitary-Adrenal System - drug effects
- Scleroderma, Systemic - drug effects
- Spleen - cytology