Inhibitory effects of antihistamines and antiserotonins on the bone marrow reactions produced by Escherichia coli endotoxin in mice

The bone marrow reactions (that is, decrease of nucleated cell counts and increase of red blood cell counts) of mouse bone were observed 1 hr after injection of endotoxin and peaked after 18 hr. These reactions were significantly inhibited when diphenhydramine, promethazine (antihistamines), chlorpromazine (antiserotonin), or cyproheptadine (antihistamine and antiserotonin) was given 30 min before endotoxin. Such bone marrow reactions were also induced with histamine or serotonin and peaked 1 hr after administration. The histamine-induced changes were inhibited by prior treatment with diphenhydramine. These reactions were also produced by injection of a small amount of both histamine and serotonin, whereas no change was found when mice were given a single injection of a larger dose of histamine or serotonin. These results indicate that histamine and serotonin released in mice at the initial stage after endotoxin synergistically trigger the bone marrow reactions, which then continue in the presence of further mediators. Antihistamines and antiserotonins are considered to hinder the whole process of reactions produced by endotoxin.