Rifampicin and dexamethasone have similar effects on macrophage phagocytosis of zymosan, but differ in their effects on nitrite and TNF-α production

• Published in: International immunopharmacology 2003-04, Vol.3 (4), p.513-522
• Main Authors: Mlambo, Godfree, Sigola, Lynette B.
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - pharmacology; Animals; Biological and medical sciences; Cells, Cultured; Dexamethasone; Dexamethasone - pharmacology; Dose-Response Relationship, Drug; Drug toxicity and drugs side effects treatment; Immunity, Innate - drug effects; Immunomodulators; Macrophage; Macrophages, Peritoneal - drug effects; Macrophages, Peritoneal - immunology; Macrophages, Peritoneal - metabolism; Male; Medical sciences; Mice; Mice, Inbred BALB C; Mifepristone - pharmacology; Miscellaneous (drug allergy, mutagens, teratogens...); Nitric oxide; Nitric Oxide - biosynthesis; Nitric Oxide - immunology; Phagocytosis; Phagocytosis - drug effects; Phagocytosis - immunology; Pharmacology. Drug treatments; Rifampicin; Rifampin - pharmacology; Spleen - cytology; Spleen - immunology; Spleen - metabolism; Tumor Necrosis Factor-alpha - biosynthesis; Tumor Necrosis Factor-alpha - immunology; Tumour necrosis factor-alpha; Zymosan - metabolism
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/S1567-5769(03)00022-5

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-α) 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-α 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.