Studies on the effects of ingestion of a single 500 mg oral dose of erythromycin stearate on leucocyte motility and transformation and on release in vitro of prostaglandin E2 by stimulated leucocytes

Abstract

Polymorphonuclear leucocyte (PMNL) and mononuclear leucocyte (MNL) migration to the leucoattractant endotoxin-activated serum as well as MNL mitogen-induced transformation were measured in normal adult volunteers before and 1 1/2 h and 96 h after the ingestion of a single oral dose of 500 mg of erythromycin stearate. Ingestion of the antibiotic was associated with a significant increase in PMNL migration at 1 1/2 h with a return to normal levels at 96 h. Slight but insignificant enhancement of MNL migration and of transformation to mitogens was detected after erythromycin. The mechanism of the slight stimulation of MNL transformation, which was consistently observed, was investigated further in vitro by measuring the effects of erythromycin base on the release of prostaglandin (PG) E2 by mitogen-stimulated MNL. Similar studies were performed using leuco-attractant-exposed PMNL. Inhibition of PGE2 release was observed for both MNL and PMNL with therapeutic concentrations of erythromycin. To assess the possible in-vivo significance of the immunopotentiating properties of the antibiotic the effect of a single intraperitoneal injection of 250, 500 or 1000 micrograms on the survival time of mice lethally infected with the erythromycin-resistant microorganism Candida albicans were investigated. Pre-treatment of the mice with erythromycin at each concentration used significantly increased the mean survival times. It is possible that these non-specific immunostimulatory properties of erythromycin potentiate in-vivo antimicrobial activity.