Alterations in hypothalamic-pituitary-adrenal function correlated with the onset of murine SLE in MRL +/+ and lpr/lpr mice.
Systemic lupus erythematosus (SLE) is a spontaneously occurring, chronic autoimmune disease that can manifest neuropsychiatric abnormalities. The pathways mediating these central changes are not known; however, neuroendocrine alterations associated with inflammation may play a role. Predisposition to and progression of autoimmune disease has been associated with altered hypothalamic-pituitary-adrenal (HPA) function and inflammation has been reported to alter hypothalamic regulation of HPA responses. We investigated whether disease progression in a murine model of systemic lupus erythematosus (MRL +/+. MRL lpr/lpr) resulted in altered expression of HPA regulatory peptides at the level of the hypothalamus and how these alterations related to circulating levels of corticosterone, corticosterone binding globulin, and autoantibody titers. We report that as MRL +/+ and MRL lpr/lpr mice age and circulating levels of autoantibodies increase, there is a decrease in hypothalamic CRH mRNA expression and finally an increase in AVP mRNA expression. We also report that associated with increased autoantibody levels, disease progression, and altered hypothalamic peptide expression there is an increase in circulating levels of corticosterone and a trend for levels of corticosterone binding globulin to decrease. Our data complement previous observations of altered peptidergic regulation of the HPA axis and increased HPA activity during chronic inflammation in exogenously induced rodent models of chronic inflammation and indicate that similar processes may occur in spontaneous murine models of SLE.
Shanks
N
N
University of Bristol, BRI Laboratories, Marlborough Street, Bristol, BS2 8HW, United Kingdom.
Moore
P M
PM
Perks
P
P
Lightman
S L
SL
D000375:Aging / Q000502:physiology; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D004247:DNA / Q000276:immunology; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism / Q000503:physiopathology*; D007031:Hypothalamus / Q000378:metabolism; D017403:In Situ Hybridization; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D051379:Mice; D019463:Mice, Inbred MRL lpr; D009479:Neuropeptides / Q000378:metabolism
D002352:Carrier Proteins; D009479:Neuropeptides; D004247:DNA; D003345:Corticosterone