Suppression of endotoxin-induced corticosterone secretion in rats by H1-antihistamine

Corticosterone (CS) secretion is stimulated in rats by an intraperitoneal injection of bacterial lipopolysaccharide (LPS) or by subjecting the animals to immobilization stress. LPS injection caused a significant increase in the lung histamine level and a sharp reduction in the number of intact peritoneal mast cells. Injection of compound 48/80, a histamine liberator, provoked an increase in the histamine levels of the blood and lung and a decrease in the number of intact peritoneal mast cells with a concomitant increase in CS secretion. Administration of histamine, at a dose of 10 mg/kg, induced a marked increase in CS release. LPS-induced CS secretion was attenuated by pretreatment with an H1-antihistamine, promethazine (PMZ), whereas an H2-antihistamine, metiamide, had no effect. In contrast, PMZ was ineffective on CS release provoked by immobilization stress. These results suggest that LPS-induced CS release is mediated, in part, by histamine released in the peripheral tissues, whereas an immobilization stress-induced increase is not mediated by the amine.