Accelerated clearance of Escherichia coli in experimental peritonitis of histamine-deficient mice

We prepared a model of experimental peritonitis by introducing Escherichia coli into the peritoneal cavity of the histamine-deficient mice generated by a disruption of the gene for histidine decarboxylase (HDC), the unique histamine-synthesizing enzyme. When we inoculated E. coli into the peritoneal cavities of the HDC^-/- (histamine-deficient) mice, they eliminated E. coli more efficiently than did the wild-type mice. Histamine was released efficiently from the peritoneal cells after E. coli inoculation in HDC^+/+ mice, although only trace amounts were detected in the peritoneal cells of HDC^-/- mice. Two histamine agonists (6-[2-(4-imidazolyl)ethylamino]-N-(4-trifluoromethylphenyl) hepatanecarboxamide (H₁) and dimaprit (H₂)) impaired the clearance of E. coli from the peritoneal cavity in HDC^-/- mice, suggesting that the activation of both H₁ and H₂ receptors suppresses the clearance. In contrast, two kinds of H₁ and H₂ receptor antagonists, cimetidine and pyrilamine, promoted the clearance of E. coli in HDC^+/+ mice. Phagocytosis appeared to be enhanced in HDC^-/- mice, since the number of neutrophils in the peritoneal cavity of HDC^-/- mice was markedly increased. This enhanced recruitment of neutrophils was suppressed in the presence of the histamine agonists, 6-[2-(4-imidazolyl)ethylamino]-N-(4-trifluoromethylphenyl)hepatanecarboxamide and dimaprit. In this report histamine was first shown to be an important mediator in an E. coli infectious peritonitis model, causing a delay in the elimination of bacteria. This also raised the possibility of the use of antihistamine drugs for bacterial infection.