Brief and long maternal separations decrease corticosterone secretion in a lupus-prone strain: Dissociation from disease-related parameters

Neonatal manipulations are known to alter the activity of the immune system and the hypothalamus–pituitary–adrenal (HPA) axis. This study was performed in order to examine whether brief and long maternal separations (BMS and LMS, respectively) interfere with the onset and development of murine lupus in NZB/NZWF1 females, and to determine whether the pattern of corticosterone (CORT) secretion throughout life is associated to the expression of the disease. Maternal separation was performed daily during postnatal days 1–14, lasting 15 min in the BMS group and 3 h in the LMS group. Blood was sampled from the retro-orbital plexus on the 9th week, and every other week, from 10th to 34th weeks of life, for detection of anti-nuclear antibodies (ANA) and anti-double-strand DNA (anti-dsDNA) antibodies, and for determination of CORT serum levels. Urine samples were collected on the 21st, 27th, 33rd and 37th weeks of life. There were no group differences in regard to disease-related parameters, but LMS females presented a tendency for late onset of anti-dsDNA antibodies. BMS and LMS mice exhibited reduced CORT levels compared to non-manipulated (NM) animals. There was a strong negative correlation between total mean CORT concentration and onset of ANA, and a strong positive correlation between total mean CORT concentration and life span only in the NM group. Neonatal manipulations appeared to eliminate these correlations; hence, both BMS and LMS modified basal CORT secretion and the association between glucocorticoids and immune activity in the NZB/NZWF1 mouse strain.