Tilmicosin and tylosin have anti-inflammatory properties via modulation of COX-2 and iNOS gene expression and production of cytokines in LPS-induced macrophages and monocytes.
Macrolides have been reported to modify the host immune and inflammatory responses both in vivo and in vitro. We examined the in vitro effect of the macrolides tilmicosin and tylosin, which are only used in the veterinary clinic, on the production of nitric oxide (NO), prostaglandin E(2) (PGE(2)) and cytokines by lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and mouse peripheral blood mononuclear cells (PBMCs). Compared with 5 microg/mL, tilmicosin and tylosin concentrations of 10 microg/mL and 20 microg/mL significantly decreased the production of 6-keto-prostaglandin F(1alpha) (6-keto-PGF(1alpha)), PGE(2), NO, tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta and IL-6, and increased IL-10 production. Cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) gene expression were also significantly reduced. These results support the opinion that macrolides may exert an anti-inflammatory effect through modulating the synthesis of several mediators and cytokines involved in the inflammatory process.
Cao
Xing-Yuan
XY
Department of Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, Beijing 100094, China.
Dong
Mei
M
Shen
Jian-Zhong
JZ
Wu
Bei-Bei
BB
Wu
Cong-Ming
CM
Du
Xiang-Dang
XD
Wang
Zhuo
Z
Qi
Yi-Tao
YT
Li
Bing-Yu
BY
D000818:Animals; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000494:pharmacology; D018942:Macrolides / Q000494:pharmacology*; D051379:Mice; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics* / Q000378:metabolism; D015645:Tylosin / Q000031:analogs & derivatives* / Q000494:pharmacology*
D052246:Cyclooxygenase 2 Inhibitors; D016207:Cytokines; D008070:Lipopolysaccharides; D018942:Macrolides; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D015232:Dinoprostone; C052319:tilmicosin; D015645:Tylosin