Corticosterone treatment of pregnant low dose endotoxin-treated rats: Inhibition of the inflammatory response

PROBLEM: Can the endotoxin-induced inflammatory response, underlying experimental pre-eclampsia, in pregnant rats be inhibited by corticosterone?

METHOD OF STUDY: On day 10 of pregnancy, rats were implanted with pellets containing 25% corticosterone and 75% cholesterol (n = 10) or with 100% cholesterol-pellets (n = 10). On day 14 of pregnancy, rats were infused with either endotoxin (1.0 mu g/kg bw) or saline. Three days later, they were sacrificed. Cryostat kidney sections were immunohistologically stained for the presence of neutrophils (PMN) and monocytes (MO) and the expression of inflammation-associated adhesion molecules.

RESULTS: In cholesterol-treated rats, endotoxin significantly increased glomerular numbers of PMN and MO, glomerular expression of ICAM-1 and VCAM-1 and glomerular numbers of LFA-1 and VLA-4-positive cells as compared with saline. Corticosterone treatment significantly inhibited glomerular infiltration of PMN, MO and LFA-1 positive cells after endotoxin infusion. It did not affect glomerular ICAM-1 or VCAM-1 expression or numbers of VLA-4 positive cells.

CONCLUSIONS: It is concluded that pre-treatment with corticosterone inhibits the low dose endotoxin-induced glomerular inflammatory reaction in pregnant rats, most likely by inhibiting LFA-1 expression, thereby decreasing the adhesiveness of inflammatory cells for activated endothelial cells.