Ribavirin shows immunomodulatory effects on activated microglia.
Abstract Ribavirin (RBV) is synthetic purine nucleoside analogue, licensed as anti-viral drug that displays immunomodulatory actions on various immune cells. Our previous ex vivo studies have demonstrated immunosuppressive effects of RBV on reactive T-lymphocytes in experimental autoimmune encephalomyelitis. Here, we examined the effects of RBV on inflammatory response of microglia. RBV potency to down-regulate microglia inflammatory response was assessed by measuring microglia cell body size, and the production of nitric oxide (NO) and pro- and anti-inflammatory cytokines. RBV exerted cytotoxic effects on LPS-stimulated microglia, leaving non-stimulated microglia unaffected. The exposure of activated microglia to RBV led to: decrease in the level of NO as a result of decreased cell number, lower average cell surface, the reduction of membrane ruffling, the suppression of interleukin-6 release and promoted interleukin-10 production. On the other hand, RBV promoted LPS-induced interleukin-1 beta release. Our results imply that RBV is a complex immunomodulator showing both anti- and pro-inflammatory effects on activated microglia.
Department for Neurobiology, Institute for Biological Research "Sinisa Stankovic", University of Belgrade , Belgrade, Republic of Serbia .
Danijela
D
Savic
Mirjana
M
Stojiljkovic
Irena
I
Lavrnja
Ana
A
Parabucki
Ivana
I
Bjelobaba
Nadezda
N
Nedeljkovic
Thomas
T
Herdegen
Sanja
S
Pekovic
D000818:Animals; D000831:Animals, Newborn; D048429:Cell Size / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D007155:Immunologic Factors / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D017628:Microglia / Q000187:drug effects* / Q000276:immunology* / Q000473:pathology; D009569:Nitric Oxide / Q000096:biosynthesis / Q000276:immunology; D061251:Primary Cell Culture; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D012254:Ribavirin / Q000494:pharmacology*
D016207:Cytokines; D007155:Immunologic Factors; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D012254:Ribavirin
Cytokines; cytotoxicity; inflammation; nucleoside analogue; primary microglia