In vitro effects of spiramycin and dirithromycin on IL1 beta production byhuman LPS-stimulated mononuclear cells

Polymorphonuclear neutrophils are the predominant cells in acute inflammato ry lesions and their functions and recruitment are regulated by cytokines, including IL1, TNF and IL8. Antibiotic modulation of inflammatory effects h as stimulated investigations of antibiotics for their potential activity as immunomodulators over their primary bactericidal or bacteriostatic activit ies. This study reports the influence of macrolides, spiramycin and dirithr omycin on IL1 beta production, Mononuclear cells, isolated from healthy hum an volunteers, were preincubated with macrolides (0.1 to 500 mu g/ml) and s timulated by Escherichia coli lipopolysaccharide. Then, IL1 beta production was detected by western blotting analysis. At therapeutic concentrations, dirithromycin and spiramycin seemed to enhance IL1 beta production by LPS-s timulated cells, with +37 per cent and +28 per cent at 1 mu g/ml respective ly. At supratherapeutic concentrations, these drugs seemed to inhibit IL1 b eta production through protein kinase C inhibition, with inhibitory concent rations 50 per cent of 378 mu g/ml for dirithromycin and 234 mu g/ml for sp iramycin. So, macrolides may modulate the host defence system through their influence on cytokine production.