Immunosuppressive phenotype of corticotropin-releasing factor transgenic mice is reversed by adrenalectomy.
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.
Boehme
S A
SA
Neurocrine Biosciences, Inc., San Diego, California 92121, USA.
Gaur
A
A
Crowe
P D
PD
Liu
X J
XJ
Tamraz
S
S
Wong
T
T
Pahuja
A
A
Ling
N
N
Vale
W
W
De Souza
E B
EB
Conlon
P J
PJ
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
D007166:Immunosuppressive Agents; D003346:Corticotropin-Releasing Hormone