Rifampicin and dexamethasone have similar effects on macrophage phagocytosis of zymosan, but differ in their effects on nitrite and TNF-alpha production.
The antibiotic rifampicin is used extensively in the treatment of mycobacterial and other infections. It has previously been suggested that rifampicin binds to and activates the glucocorticoid receptor potentially leading to pharmacological glucocorticoid-like effects such as host immunosuppression (Calleja et al.). This study compares the effects of rifampicin with the synthetic glucocorticoid dexamethasone, on macrophage phagocytosis of zymosan particles and production of nitric oxide (NO) and tumour necrosis factor-alpha (TNF-alpha) by splenocytes or macrophages. Rifampicin and dexamethasone, partially suppressed zymosan phagocytosis by macrophages, respectively, and both effects were ameliorated by the glucocorticoid receptor antagonist RU486. In other experiments, rifampicin had no effects on NO responses; however, dexamethasone inhibited NO in an RU486-sensitive manner. At high doses, rifampicin moderately suppressed TNF-alpha while dexamethasone inhibited it in a dose-dependent manner, which was ameliorated by the presence of RU486. These findings suggest that rifampicin has differential immunomodulatory effects on these innate immune mechanisms.
Mlambo
Godfree
G
Department of Immunology, Faculty of Medicine, University of Zimbabwe, PO Box A 178 Avondale, Harare, Zimbabwe.
Sigola
Lynette B
LB
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007113:Immunity, Innate / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015735:Mifepristone / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000276:immunology; D010587:Phagocytosis / Q000187:drug effects* / Q000276:immunology; D012293:Rifampin / Q000494:pharmacology; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000276:immunology; D015054:Zymosan / Q000378:metabolism
D000276:Adjuvants, Immunologic; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D015735:Mifepristone; D003907:Dexamethasone; D015054:Zymosan; D012293:Rifampin