Alterations in hypothalamic-pituitary-adrenal function correlated with theonset of murine SLE in MRL plus / plus and lpr/lpr mice

Systemic lupus erythematosus (SLE) is a spontaneously occurring, chronic au toimmune disease that can manifest neuropsychiatric abnormalities. The path ways mediating these central changes are not known; however, neuroendocrine alterations associated with inflammation may play a role. Predisposition t o and progression of autoimmune disease has been associated with altered hy pothalamic-pituitary-adrenal (BPA) function and inflammation has been repor ted to alter hypothalamic regulation of MPA responses. We investigated whet her disease progression in a murine model of systemic lupus erythematosus ( MRL +/+. MRL lpr/lpr) resulted in altered expression of HPA regulatory pept ides 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 hypo thalamic CRH mRNA expression and finally an increase in AVP mRNA expression . We also report that associated with increased autoantibody levels, diseas e progression, and altered hypothalamic peptide expression there is an incr ease in circulating levels of corticosterone and a trend for levels of cort icosterone binding globulin to decrease. Our data complement previous obser vations of altered peptidergic regulation of the PIPA axis and increased HP A activity during chronic inflammation in exogenously induced rodent models of chronic inflammation and indicate that similar processes may occur in s pontaneous murine models of SLE. (C) 1999 Academic Press.