難治性下気道感染症におけるエリスロマイシンの好中球機能に及ぼす影響--緑膿菌への作用と気管支肺胞洗浄液の検討
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The & ldquo;low dose and long term & rdquo; erythromycin (EM) therapy has been reported as effective (or useful) in chronic respiratory tract disease with pseudomonas (P.) infection including diffuse panbronchiolitis (DPB), however the mode of action is still obscure. Therefore in this study we have examined the effect of EM on the interaction between <I>P. aeruginosa</I> and human polymorphonuclear leukocyte (PMN) <I>in vitro</I>.<BR>The efficiency of intracellular killing and the ability of superoxide production were employed to evaluate the PMN functions.<BR>For the first step, the following results were obtained;<BR>1) Pretreatment of PMN with 20 & mu;g/ml EM did not affect the killing ability of PMNs against opsonized P. aeruginosa of standard and clinical isolate from DPB patient.<BR>2) Superoxide production from PMNs was observed by phagocytosis of <I>P. aeruginosa</I> in the presence of serum. This was not affected by exposure of PMNs to 20 & mu;g/ml EM even with increased ratios of bacteria to cells.<BR>3) Pretreatment of <I>P. aeruginosa</I> with 20 & mu;g/ml EM before opsonization enhanced the killing ability of PMNs in both standard and clinical isolate.<BR>4) Pretreatment of <I>P. aeruginosa</I> with 20 & mu;g/ml EM resulted in no effect on superoxide production from PMNs by phagocytosis of the bacteria.<BR>These results indicate that EM may modify a certain step of the interaction between bacteria and intracellular host defence mechanisms. Therefore for the second step, we have investigated the susceptibility of EM-exposed bacteria to killing by the cell free (glucose oxidase-glucose) system, which will detect the enzymatic generation of hydrogen peroxide (H<SUB>2</SUB>O<SUB>2</SUB>).<BR>The following results were observed;<BR>1) EM-exposed bacteria was more susceptible to killing than control bacteria.<BR>2) The enhanced susceptibility was not dependent on the continueous presence of EM.<BR>This enhanced efficiency indicates that EM may affect the bacteria to become more susceptible to oxygen dependent killing mechanisms of the PMNs.<BR>Concerning the host factors, we have also investigated the influence of supernatant of BALF on PMN's function. Specimens were from five patients with DPB.<BR>The results were as follows;<BR>1) The superoxide production from PMNs was only observed by the presence of BALF supernatant from DPB but not from sarcoidosis, pneumonia, idiopathic pulmonary fibrosis.2) BALF supernatants from two DPB patients after a long term EM treatment could not induce superoxide production from PMNs.<BR>3) Chemotaxis and killing of PMNs have been enhanced in the presence of BALF supernatant from DPB.<BR>These results suggest the presence of some kind of neutrophil activating factor in BALF from DPB patients, and EM may play a role through such kinds of cytokines in an unresolved manner. Further studies are warranted to disclose the pathogenesis of chronic pulmonary infection in DPB and the effective mechanism of EM.
- 日本感染症学会の論文
日本感染症学会 | 論文
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