title: Immunosuppressive phenotype of corticotropin-releasing factor transgenic mice is reversed by adrenalectomy.
abstract: Stress elicits a wide range of physiological changes involving the nervous, endocrine, and immune systems. Corticotropin-releasing factor (CRF) plays a key role in orchestrating this response, activating both the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis, resulting in release of corticosteroids. The present study examines the immunological phenotype and responsiveness of CRF-transgenic (CRF-Tg) mice. The immune system of the CRF-Tg animals has profound changes compared to littermate controls, including a marked reduction in both cell number and immune responsiveness. There were also phenotypic changes in the lymphocytic composition of the various lymphoid organs, most notably in the spleen, where CRF-Tg mice had a greater percentage of T lymphocytes compared to littermate controls. Adrenalectomy of CRF-Tg reversed the immunological phenotype observed and restored immune responsiveness. These results demonstrate that CRF overexpression leads to profound impairment on lymphocyte development and function mediated via corticosteroids.
authors.affiliation: Neurocrine Biosciences, Inc., San Diego, California 92121, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Boehme
authors.forename: A
authors.initials: A
authors.lastname: Gaur
authors.forename: P D
authors.initials: PD
authors.lastname: Crowe
authors.forename: X J
authors.initials: XJ
authors.lastname: Liu
authors.forename: S
authors.initials: S
authors.lastname: Tamraz
authors.forename: T
authors.initials: T
authors.lastname: Wong
authors.forename: A
authors.initials: A
authors.lastname: Pahuja
authors.forename: N
authors.initials: N
authors.lastname: Ling
authors.forename: W
authors.initials: W
authors.lastname: Vale
authors.forename: E B
authors.initials: EB
authors.lastname: De Souza
authors.forename: P J
authors.initials: PJ
authors.lastname: Conlon
mesh_terms: D000315:Adrenalectomy; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000276:immunology*; D005260:Female; D016130:Immunophenotyping; D007166:Immunosuppressive Agents / Q000037:antagonists & inhibitors / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic
chemical_list: D007166:Immunosuppressive Agents; D003346:Corticotropin-Releasing Hormone