Macrolides and immunity: effects of erythromycin and spiramycin on human mononuclear cell proliferation

Macrolides are actively concentrated by leucocytes. The dose-effect responses of spiramycin (Sp) and erythromycin (Er) on phytohaemagglutinin (PHA) and pokeweed mitogen (PWM) stimulated human mononuclear leucocytes (MNL) were studied. Cell viability was not altered at any antibiotic concentration (1-100 mg/l). Both Sp and Er showed dose-related inhibition of the proliferative response of PHA and PWM stimulated MNL. Very marked effects were observed at high antibiotic concentrations and the effects observed at low concentrations (1-10), although small, were also significant. Similar results were observed for the mitogen PWM. A decrease in tritiated thymidine (3H-TdR) incorporation occurred only if Sp and Er were added during the first 8 h of culture. Sp and Er also induced a decrease in tritiated uridine (3H-UdR) uptake. These data suggest that Sp and Er interfered with an early event in the cell cycle. However Sp did not affect PHA binding to MNL. The clinical significance of these findings is discussed.