ANALYSIS OF THE LONG-TERM TREATMENT WITH ERYTHROMICIN IN CHRONIC LOWER RESPIRATORY TRACT INFECTIONS : Ⅱ. EFFECTS OF ERYTHROMYCIN ON MURINE POLYMORPHONUCLEA LEUKOCYTES AND IMMUNOCOMPETENT CELLS

The present study was carried out to analyze the effects of erythromycin on functions of polymorphonuclear leukocytes (PMN) and immunocompetent cells in mice. Administration of erythromycin (EM) reduced phagocytic activity as determined by chemiluminescence, although chemotaxsis and elastase production of PMN were not affected. These were consistent with results obtained from PMN of EM-treated patients with chronic lower respiratory infections. However, serum of EM-treated mice exhibited suppressive activity to mitogenic activity of recombinant interleukin 1 (rIL-1), when serum was prepared from mice 2h after intravenous injection of heat-killed Pseudomonas aeruginosa. Inhibition of IL-1 activity by this serum was neutralized by anti-mouse α＿1-antitrypsin (α＿1-AT) antiserum to a significant extent. Furthermore, mouse splenocytes cultured with several concentrations of EM produced higher levels of IL-2 upon stimulation with concanavaline A (Con A). IL-2 production by splenocytes increased in proportion to increasing doses of EM (2-5 μg/ml), but EM suppressed IL-2 production at doses higher than 10 μg/ml. These results were consistent with the results of Con A-induced blastogenesis of splenocytes. Additionally, IL-1 production by PMN and alveolar macrophage was also enhanced by EM in the dose range of 2-5 μg/ml. To analyze the kinetics of production of IL-1 suppressive factor in serum, supernatant fluids from cultures of mouse hepatocytes with EM were tested for α＿1-AT activity and IL-1 inhibitory activity. Upon stimulation with IL-1, cultured hepatocytes produced α＿1-AT in the presence of EM (5-10 μg/ml) higher than did hepatocytes cultured without EM. Furthermore, supernatant fluids of hepatocytes cultured with EM exhibited suppressive activity to IL-1. These results suggest that EM can exert regulatory functions in host defense mechamsms.