Effect of erythromycin on neutrophil function in chronic respiratory tract diseases with Pseudomonas infection

Abstract

The "low dose and long term" 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 P. aeruginosa and human polymorphonuclear leukocyte (PMN) in vitro. The efficiency of intracellular killing and the ability of superoxide production were employed to evaluate the PMN functions. For the first step, the following results were obtained; 1) Pretreatment of PMN with 20 micrograms/ml EM did not affect the killing ability of PMNs against opsonized P. aeruginosa of standard and clinical isolate from DPB patient. 2) Superoxide production from PMNs was observed by phagocytosis of P. aeruginosa in the presence of serum. This was not affected by exposure of PMNs to 20 micrograms/ml EM even with increased ratios of bacteria to cells. 3) Pretreatment of P. aeruginosa with 20 micrograms/ml EM before opsonization enhanced the killing ability of PMNs in both standard and clinical isolate. 4) Pretreatment of P. aeruginosa with 20 micrograms/ml EM resulted in no effect on superoxide production from PMNs by phagocytosis of the bacteria. 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 (H2O2). The following results were observed; 1) EM-exposed bacteria was more susceptible to killing than control bacteria.(ABSTRACT TRUNCATED AT 250 WORDS)