Abstract
Early-life exposure to bacterial endotoxins, such as lipopolysaccharides (LPS), can provide neuroprotection against experimental autoimmune encephalomyelitis (EAE) during adulthood, possibly through altering the responsiveness of the immune system. Here, we show that exposure of LPS to neonatal rats resulted in a sustained elevation of corticosterone level in urine when compared with saline-treated rats, and that the high level of urine corticosterone was maintained during the progression of EAE (P<0.05). This high level of production of corticosterone plays an important role in altering the predisposition to EAE-induced neuroinflammation, as a positive correlation occurred between the concentration of urine corticosterone and the increased apoptotic CD4(+) T cells from the peripheral blood. LPS-treated rats also showed a reduced number of CD3(+) T cells in the spinal cord. The splenic antigen-presenting cells showed a reduced expression of MHC II during EAE development in LPS-exposed rats when compared with rats exposed to the saline-treated control. Together, these findings suggest that treating neonatal rats with LPS evokes a sustained elevation of glucocorticoid, which may suppress immune response during EAE by increasing apoptosis of CD4(+) T cells and reducing the expression of MHC II on antigen-presenting cells. Therefore, exposing neonates to bacterial endotoxin may further be developed as an immunization strategy to prevent human multiple sclerosis and other inflammatory brain diseases.