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

PROBLEM: Can the endotoxin-induced inflammatory response, underlying experi mental pre-eclampsia, in pregnant rats be inhibited by corticosterone? METHOD OF STUDY: On day 10 of pregnancy, rats were implanted with pellets c ontaining 25% corticosterone and 75% cholesterol (n = 10) or with 100% chol esterol-pellets (n = 10). On day 14 of pregnancy, rats were infused with ei ther endotoxin (1.0 mu g/kg bw) or saline. Three days later, they were sacr ificed. Cryostat kidney sections were immunohistologically stained for the presence of neutrophils (PMN) and monocytes (MO) and the expression of infl ammation-associated adhesion molecules. RESULTS: In cholesterol-treated rats, endotoxin significantly increased glo merular numbers of PMN and MO, glomerular expression of ICAM-1 and VCAM-1 a nd glomerular numbers of LFA-1 and VLA-4-positive cells as compared with sa line. Corticosterone treatment significantly inhibited glomerular infiltrat ion of PMN, MO and LFA-1 positive cells after endotoxin infusion. It did no t affect glomerular ICAM-1 or VCAM-1 expression or numbers of VLA-4 positiv e cells. CONCLUSIONS: It is concluded that pre-treatment with corticosterone inhibit s the low dose endotoxin-induced glomerular inflammatory reaction in pregna nt rats, most likely by inhibiting LFA-1 expression, thereby decreasing the adhesiveness of inflammatory cells for activated endothelial cells.