1019: Progesterone attenuates brain inflammatory response and protects the brain from inflammation-induced immature myeloid cells increase

Abstract

Pregnancy is a challenge for the maternal immune system since it has to defend against pathogens while tolerating alloantigenic fetal tissue. Little is known about maternal brain immune system during pregnancy. During pregnancy there is a marked increase in endogenous progesterone (PRO) and PRO supplementation is used for prevention of preterm birth. We sought to determine the maternal brain immune response to inflammation in pregnant (P) and non-pregnant (NP) mice and whether PRO supplementation attenuates this response. NP & P mice were pretreated with vaginal PRO or carrier from E13-E16. Lipopolysaccharide (LPS 30μg) or vehicle were administered intraperitoneally at E15 & E16. Serum was analyzed for IL-6 levels by ELISA. Brain was analyzed for nNOS, NFkB, IL-6 & TNF-a levels by western blot. Brain immature myeloid cells (IMC; CD45high, CD11b+, Gr1+) as % of CD45high hematopoietic brain cells and microglial (CD45low cells) activity as medial CD45 intensity was analyzed by FACS. LPS significantly increased brain nNOS, NFkB, IL-6 & TNF-a protein brain levels in NP & P mice. PRO pretreat ment significantly reduced nNOS and NFkB brain levels following LPS treatment in both groups. In NP mice, LPS treatment significant increased brain IMC population, and PRO pretreatment reduced the increase. In P mice, neither LPS nor LPS & PRO altered the brain IMC population. LPS led to a significant increase in microglial activity both groups. PRO pretreatment led to significant decrease in microglial activity in P mice. In NP mice, there was a trend but it did not reach statistical significance. PRO had no effect on serum IL-6 levels in both groups. PRO attenuates the inflammatory response in the brain in NP & P mice but had no effect on systemic (IL-6) inflammation. LPS increased brain IMC population in NP mice but not in P mice and PRO pretreatment reduced the IMC increase. These results suggest that endogenous PRO during pregnancy may protect the brain from LPS-induced central inflammation.View Large Image Figure ViewerDownload Hi-res image Download (PPT)