EFFECT OF ANTILEUKOCYTE ADHESION MOLECULE ANTIBODIES, NITRIC-OXIDE SYNTHASE INHIBITOR, AND CORTICOSTEROIDS ON ENDOTOXIN-SHOCK IN MICE

We compared the therapeutic effects of antileukocyte adhesion molecule antibodies (mAbs), a nitric oxide (NO) synthase inhibitor (monomethyl -L-arginine, NMLA), and methylprednisolone (MP) on experimental endoto xin-induced shock in mice, Lipopolysaccharide (LPS, 30 mg/kg) was admi nistered to ICR mice intraperitoneally, While 1 mg/kg mAb, 5-20 mg/kg NMLA, or 30 mg/kg MP was administered intravenously. The placebo group received phosphate-buffered saline. The survival rate of the placebo group 48 h after LPS injection was 36%. The administration of anti-CD1 1a, anti-CD18, anti-lectin cell adhesion molecule-1 (anti-LECAM-1), an d MP increased the survival rate to 70, 62, 64, and 100%, respectively ; however, NMLA had no significant effect. A FACS analysis revealed th at the CD18 expression of granulocytes increased 12-fold within 30 min after LPS administration. MP significantly suppressed its expression. The plasma level of nitrate/nitrite increased from 20 to 260 and 1000 mu M 4 and 16h, respectively, 20 mg/kg NMLA abolished NO production a t 4h, while MP inhibited it for up to 16 h. The hepatic malondialdehyd e level increased from 0.50 to 2.46 nmol/mg protein at 4h. Administrat ion of anti-CD18 and MP reduced the level to 1.80 and 1.41 nmol/mg pro tein, respectively, whereas NMLA did not affect it. The mAbs and MP we re concluded to be useful agents for endotoxin shock. The abolition of NO production had little influence on the hepatic cellular injury ass ociated with endotoxemia.