Mechanism by which methylprednisolone inhibits acute immune complex-induced changes in vascular permeability.

Intravital microscopy was used to quantitate protein leakage which resulted from the deposition of immune complexes in the vasculature of the rat cremaster muscle. Immune complex deposition was initiated by the addition of 80 micrograms/ml of ovalbumin to the bath surrounding the muscle, followed by the intravenous administration of antiovalbumin. Administration of 25 mg/kg of antiovalbumin produced significant leakage of protein from the third-order venules, while 7.5 and 2.5 mg/kg had no effect. Administration of methylprednisolone (MP), 30 mg/kg, 1 h prior to the deposition of immune complexes significantly inhibited protein leakage. In separate experiments, MP inhibited intradermal edema formation and protein exudation induced in rats by histamine, platelet activating factor, or C5a. However, MP had no effect on protein exudation or edema produced by xanthine oxidase or glucose oxidase. Intravenous administration of MP inhibited the ability of polymorphonuclear leukocytes (PMNs) to phagocytize bacteria, but failed to alter hydrogen peroxide production. These results suggest that MP prevents acute changes in vascular permeability following immune complex deposition by inhibiting the effects of soluble mediators of edema on vascular endothelium and by inhibiting PMN phagocytosis.