Antileprotic Agents (Clofazimine)のらい患者食細胞に対する作用機序とらいの発生病理についての示唆

抄録

The capacity to generate oxygen intermediates (OI; O₂-, H₂O₂, OH·) and chemiluminescence, and to release lysosomal enzyme (lysozyme, β-glucuronidase), and the superoxide dismutase (SOD) activity of polymorphonuclear leukocytes (PMNL) and monocytes from 14 leprotic patients manifesting a bacillary index above 2.2 was examined to determine the action mechanism of clofazimine. Significantly enhanced SOD activity, and a decrease in O₂-, and OH· production were observed in the patients with more than 4 years history. The generation of OH· was significantly increased, in a dose dependens manner, by clofazimine, with a subsequent decrease in H₂O₂ and chemiluminescence, while SOD activity of the PMNLs and monocytes was not affected. In the medium supplemented with FeSO₄ or EDTA containing Fe⁺⁺, OH· production was further markedly elevated by the drug. Phagocytic SOD in PMNLs and monocytes of the pasients was both host- and bacillus-derived, because the presence of potassium cyanide, to which human-derived cuprozic SOD is susceptible, did not completely abrogate SOD activity. The difficulty in treating leprosy may be partly ascribable to the decreased phagocytic OH· generation in this disease, which in leprosy patients is induced by increased Hansen bacillus-derived SOD uptaken by the patients. Clofazimine may be effective in leprosy by potentiating the catalyzing activity of Fe⁺⁺ which facilitates Haber-Weiss reaction to increase OH· formation from H₂O₂, without affecting SOD activity which was enhanced by their uptake.