The Effect of Antihistamine of Endotoxin-induced Acute Lung Injury / 결핵

ABSTRACT

BACKGROUND: Sepsis-induced acute lung injury (ALI) is caused by many cellular and humoral mediators induced by an endotoxin. Histamine, which is widely distributed in the lungs and has been considered as an importa nt mediator of sepsis. It increases P-selectin expression on the endothelial cell surfaces and induces IL-8 secretion. Therefore, an endotoxin-induced histamine may be related to neutrophil-mediated ALI by inducing the migration and activation of neutrophils in the lung tissue. However, the role of endogenous histamine in endotoxin-induced ALI had not been clarified. The purpose of this study was to investigate how endotoxin-induced ALI is influenced by endogenous histamine and to identify the possible mechanism of action. METHODS: The study consisted of 4 groups using Sprague-Dawley rats 1) control group, where the rats were infused intratracheally by normal saline, 2) an endotoxin group, where lipopolysaccharide (LPS) was administered intratracheally 3) the H2 receptor antagonist-treated group (H2 group) and 4) the H1 receptor antagonist-treated group (H1 group), where H2 receptor blocker (ranitidine) and H1 receptor blocker (pyrilamine) were co-treated intravenously with the intratracheal administration of an endotoxin. The lung leak index using I125-BSA, the total protein and LDH concentration in the lung lavage fluid, myeloperoxidase (MPO) activity in the lung tissue, the pathologic score and the total number of neutrophils, TNF-alpha, IL-Ibeta and IL-10 in lung lavage (BAL) fluid were measured in each group as the indices of lung injury. RESULTS: Compared to the control group, the endotoxin group exhibited significant increasis in all lung injury indices. Significant reductions in the encotoxin-mediated increases in lung leak index (p<0.05) were observed in both the H1and H2 groups. In addition, the total protein (p<0.05) and LDH concentration (p<0.05) in the BAL fluid were also lower in the H2 group compared to the endotoxin group. However, there was no change in the MPO activity in the lung tissue, the pathologic score and the total number of neutrophils in the BAL fluid in both the H2and H1 groups compared to the endotoxin group. The increases in TNF-alpha, IL-Ibeta and IL-10 concentrations in the BAL fluid observed in the endotoxin group were not reduced in the H2and H1 groups. CONCLUSION: Antigistamine attenuated the enhanced alveolar-capillary permeability induced by the endotoxin via the H2 receptor. However the attenuation mechanism may not be related to the pathogenesis of neutrophil dependent lung injury.