title: Disturbed immuno-endocrine communication via the hypothalamo-pituitary-adrenal axis in autoimmune disease.
abstract: Previous studies in our laboratory demonstrated an altered immuno-endocrine feedback communication via the hypothalamo-pituitary-adrenal (HPA) axis, which may be an important modulatory factor in the development of spontaneous autoimmune thyroiditis in Obese strain (OS) chickens. These birds show a significantly lower, or even absent, increase in serum glucocorticoid levels in response to an intravenous injection of antigen or conditioned medium (CM) from mitogen-stimulated spleen cells known to contain glucocorticoid-increasing factors (GIFs), notably interleukin-1 (IL-1). The present study was aimed at investigating this feedback regulation in animal models with spontaneous systemic autoimmune diseases, such as the UCD-200 chicken, which serves as a model for human scleroderma, and various murine lupus models. In contrast to OS chickens, UCD-200 chickens displayed a nearly normal plasma corticosterone surge in response to CM, and IL-1 was again identified as the primary GIF in CM. Recombinant IL-1 also induced a drastic increase in plasma corticosterone levels in various strains of normal mice. A similar increase was observed in the bacterial lipopolysaccharide-resistant C3H/HeJ strain, thus excluding the possibility of bacterial endotoxin contamination. However, in young lupus-prone (NZB/W)F1 and MRL/MP-lpr mice, a significantly lower increase in plasma corticosterone levels was observed after injection of recombinant IL-1, suggesting a deficient immuno-endocrine communication via the HPA loop in this instance as well. Detailed studies to identify further cytokines with GIF activity in the avian and murine systems showed that both IL-6 and tumor necrosis factor-alpha could induce increased plasma corticosterone levels in mice, but not in chickens. IL-3, IL-8, transforming growth factor-beta, interferon-gamma and granulocyte-macrophage colony-stimulating factor were devoid of GIF activity in both chickens and mice.
authors.affiliation: Institute for General and Experimental Pathology, University of Innsbruck School of Medicine, Austria.
authors.forename: Y
authors.initials: Y
authors.lastname: Hu
authors.forename: H
authors.initials: H
authors.lastname: Dietrich
authors.forename: M
authors.initials: M
authors.lastname: Herold
authors.forename: P C
authors.initials: PC
authors.lastname: Heinrich
authors.forename: G
authors.initials: G
authors.lastname: Wick
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000503:physiopathology*; D002645:Chickens; D003345:Corticosterone / Q000097:blood; D016207:Cytokines / Q000502:physiology; D005260:Female; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D007375:Interleukin-1 / Q000502:physiology; D008180:Lupus Erythematosus, Systemic / Q000503:physiopathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010913:Pituitary-Adrenal System / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D016207:Cytokines; D007375:Interleukin-1; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D003345:Corticosterone