17. Maternal immune activation in late gestation increases corticosterone secretion and stimulates Th1 immunity in male mice offspring

Abstract

Maternal infection during pregnancy is considered an environmental risk factor to emergence of many disorders in later life, including abnormal function of the HPA axis and Th1/Th2 cytokine balance. Thus, the aim of the present study was to evaluate the effects of prenatal exposure to LPS on corticosterone secretion and immune response to acute restraint stress in male mice offspring. Lipopolysaccharide (LPS) (E.coli serotype 0127:B8) was administered ip to pregnant Swiss mice at a dose of 120 μg/kg on GD 17. At adulthood, male offspring was distributed in three experiments: (1) plasmatic corticosterone determination before and after acute restraint stress (2 h); (2) determination of oxidative burst and phagocytosis of blood neutrophils, fenotyping of dendritic cells and Th1/Th2 cytokine production by cultured splenocytes immediately after acute stress; (3) development of delayed type hypersensitivity (DTH). The LPS treated offspring showed: (1) increased corticosterone secretion after acute stress, when compared to baseline and saline stressed offspring; (2) enhancement of the IL-12 and IFN-gama production by cultured splenocytes, despite no differences were found on neutrophil and dendritic cells activity; (3) increased DTH. Our results indicate that maternal immune activation elicits increased corticosterone secretion and stimulates the Th1 immunity by the male offspring. Taken together, these evidences support the notion that inflammatory conditions during fetal development modulate both the endocrine response to stressors and the cell-mediated immunity.