<原著>結核性肺病巣に及ぼす INH の効果とその作用機序

Abstract

It has already been made clear clinically and empirically that compared with SM and other antituberculosis drugs INH accelerates remarkably the absorption and cicatrization of tuberculous lesions. In general this is attributed to the excellent antituberculous effect of INH, to the fact that it is comparatively free from secondary effects, and to the fact that with its advent it has become possible to carry out a truly effective long-term chemotherapy. Teramatsu and others took note of the particular accelerating effect of INH on the absorption and cicatrization of tuberculous lesions, and inferred that INH acts on tubercle bacilli in such a way that the decrease of bacillar lipid takes place. The findings of Teramatsu et al that formed the basis for this inference, however, are not wholly reliable and seem to require reconsideration in various respects. The purpose of this study is to supplement and further verify these findings. In Chapter I, for the purpose of confirming anew the accelerating effect of INH on the absorption and cicatrization of tuberculous pulmonary lesions, mainly lesions obtained from resected lungs of cases treated for the first time singly with INH and SM were studied and compared pathohistologically. Teramatsu uses as his index for measuring the stabilization of the lesion and the state of absorption and cicatrization the degree of formation of his so-called outer stratified tissue in the capsule of lesion, but we use as our index the so-called inner fibrous layer of Yamazaki which corresponds roughly with the metachromasia positive layer of Teramatsu's outer stratified tissue. This is because it has been made clear by Yamazaki that the inner fibrous layer is better as an index for studies of this kind. In lesions of cases treated for the first time singly with INH, the formation of the inner fibrous layer was poor in many lesions. The proliferation of epithelioid cells was remarkable, and granular tissue accompanied by abundant capillary vessels was observed here and there to invade the caseous area. That is, the indication of the absorption and cicatrization of the lesion was clearly observed. On the other hand, in lesions of cases treated for the first time singly with SM, the formation of the inner fibrous layer was remarkable in most lesions, and there was a strong indication of the stabilization of the lesions. In Chapter II, for the purpose of confirming these findings by animal experiment, lesions treated with SM or INH and lesions made with bacilli treated beforehand with INH were studied and compared. Compared with the control group, in lesions treated after infection with SM the the perifocal inflammation was remarkable inhibited, the lesion was considerably localized, and collagen fibre layer covering the caseous necrotized part was observed. On the other hand, in lesions treated with INH and in lesions made using bacilli treated beforehand with INH, a proliferation of epithelioid cells was observed. Necrotized lesions were small in number, and the capsula was not formed in most lesions. Considering that such effects of INH are a result of the decrease of bacillar lipid caused by the action of INH on tubercle bacilli, tuberculoid lesion were made using tubercle bacilli which were extracted lipid with ether. In the lesion thus obtained, no necrosis or capsulation of lesion was observed. The proliferation of epithelioid cells was remarkable. In fact findings suggesting epithelioid cell tubercle were obtained. Tuberculoid lesions producted with tubercle bacilli extracted lipid are very much like lesions treated in various ways with INH, which seems to suggest strongly that INH causes the decrease of lipid of bacilli. In Chapter III, the lipid volume of tubercle bacilli treated with INH or SM was calculated by applying Folch's method. In bacilli treated with INH the lipid volume had decreased. In Chapter IV these results were summarized and the mechanism of the action of INH was considered. The