SUPPRESSION OF EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS BY RESTRAINTSTRESS - SEX-DIFFERENCES

We have recently reported that female Lewis rats exhibit significantly higher basal circadian levels of corticosterone (Cort) than male Lewi s rats. The studies reported here were designed to explore whether mal e and female Lewis rats demonstrate a differential suppression of expe rimental autoimmune encephalomyelitis (EAE) following exposure to an i dentical regimen of repetitive restraint stress. Rats were restrained for 1 or 9 h/day beginning 5 days before myelin basic protein (MBP) ch allenge and extending through the recovery period (18 days post challe nge). Both clinical signs and histopathological changes of EAE were mo re significantly suppressed in 9-h-stressed females relative to male L ewis rats. Investigation of the mechanism underlying the stress-induce d suppression of EAE revealed that restraint stress did not alter the clinical course of EAE in rats challenged with MBP 68-88 encephalitoge nic peptide, suggesting that restraint stress may affect processing an d/or presentation of the MBP molecule. Stressed rats exhibited decreas ed interleukin-2 and interferon y production, and the frequency of MBP -reactive lymphocytes was reduced in comparison to non-stressed rats. Finally, repetitive restraint stress had no effect on blood-spinal cor d permeability during EAE. The results presented here underscore the i mportance of such experimental variables as sex, strain, time of day, and the kinetics of immune response development.