In vitro effects of spiramycin and dirithromycin on IL1 beta production by human LPS-stimulated mononuclear cells.
Polymorphonuclear neutrophils are the predominant cells in acute inflammatory lesions and their functions and recruitment are regulated by cytokines, including IL1, TNF and IL8. Antibiotic modulation of inflammatory effects has stimulated investigations of antibiotics for their potential activity as immunomodulators over their primary bactericidal or bacteriostatic activities. This study reports the influence of macrolides, spiramycin and dirithromycin on IL1 beta production. Mononuclear cells, isolated from healthy human volunteers, were preincubated with macrolides (0.1 to 500 micrograms/ml) and stimulated 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-stimulated cells, with +37 per cent and +28 per cent at 1 microgram/ml respectively. At supratherapeutic concentrations, these drugs seemed to inhibit IL1 beta production through protein kinase C inhibition, with inhibitory concentrations 50 per cent of 378 micrograms/ml for dirithromycin and 234 micrograms/ml for spiramycin. So, macrolides may modulate the host defence system through their influence on cytokine production.
Moutard
I
I
Laboratoire de Pharmacologie, Pharmacocinétique et Pharmacie Clinique, Faculté des Sciences Pharmaceutiques et Biologiques de Lille, France.
Gressier
B
B
Bonte
F
F
Dine
T
T
Brunet
C
C
Luyckx
M
M
Ballester
L
L
Cazin
M
M
Cazin
J C
JC
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004917:Erythromycin / Q000031:analogs & derivatives / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D018942:Macrolides; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D015572:Spiramycin / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D020672:I-kappa B Proteins; D007375:Interleukin-1; D008070:Lipopolysaccharides; D018942:Macrolides; D016328:NF-kappa B; C053853:dirithromycin; D004917:Erythromycin; D015572:Spiramycin; D011493:Protein Kinase C