Possible role of glucocorticoids in a complement-activated state induced by cobra venom factor in rats

Activation of the complement system of adrenalectomized rats with an injection of cobra venom factor (CVF) caused death of the rats within 2.5 h. Morphologically, this activation provoked distinct congestion of the gastric glandular mucosa and pulmonary leukostasis. Pretreatment of the animals with dexamethasone abolished the undesirable responses completely. Injection of CVF to intact rats produced only slight responses, but caused a marked increase in the serum levels of corticosterone. Dexamethasone was found to be replaced by promethazine (H1-antihistamine) or dimethylsulphoxide (scavenger of hydroxyl radicals) but not by indomethacin, ibuprofen (cyclo-oxygenase inhibitors), deferoxamine mesylate (iron chelator) or imidazole (thromboxane synthetase inhibitor). These results suggest that glucocorticoids protect the animals from the adverse effects of excessive complement activation and that they act as an inhibitor of the production or action of histamine and toxic oxygen products induced by complement activation.