Differing effects of clarithromycin and azithromycin on cytokine production by murine dendritic cells.
Summary The macrolide antibiotics are now well known to have anti-inflammatory effects. Because dendritic cells (DCs) orchestrate immune responses, we examined the in vitro effects of clarithromycin (CAM), azithromycin (AZM) and midecamycin (MDM) on the expression of co-stimulatory molecules and production of cytokines [interleukin (IL)-10, IL-6, interferon (IFN)-gamma, IL-12p40, tumour necrosis factor (TNF)-alpha] of murine bone marrow-derived DCs by lipopolysaccharide (LPS) stimulation. A 15-membered macrolide, AZM, and a 14-membered macrolide, CAM, significantly enhanced the intensity of a co-stimulatory molecule, CD80, on DCs but not CD86 and CD40. AZM significantly increased the production of IL-10 and CAM significantly inhibited the production of IL-6 by DCs. However, a 16-membered macrolide, MDM, did not have any significant effect on these surface markers and cytokine productions. Moreover, AZM increased IL-10 and CAM decreased IL-2 productions significantly, when naive T cells derived from spleen were co-cultured with DCs treated in advance with LPS and these macrolides. These findings suggest that 14-membered and 15-membered, but not 16-membered macrolides play as anti-inflammatory agents, at least in part, through modulating the functions of DCs. However, each macrolide affects them in different ways.
Sugiyama
K
K
Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan.
Shirai
R
R
Mukae
H
H
Ishimoto
H
H
Nagata
T
T
Sakamoto
N
N
Ishii
H
H
Nakayama
S
S
Yanagihara
K
K
Mizuta
Y
Y
Kohno
S
S
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015703:Antigens, CD / Q000378:metabolism; D017963:Azithromycin / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000276:immunology; D002478:Cells, Cultured; D017291:Clarithromycin / Q000494:pharmacology*; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis*; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D005260:Female; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000276:immunology
D000900:Anti-Bacterial Agents; D015703:Antigens, CD; D016207:Cytokines; D008070:Lipopolysaccharides; D017963:Azithromycin; D017291:Clarithromycin