Effect of thalidomide on nitric oxide production in lipopolysaccharide-activated RAW 264.7 cells.
Thalidomide is anti-inflammatory under some conditions, yet has been reported to up-regulate Th1 (T helper 1) immunity measured by increased IL-2 (Interleukin-2) and gamma interferon. The authors have assessed the effect of thalidomide and analogues, di- and tri-thiothalidomide, on a lipopolysaccharide (LPS) activated macrophage cell line (RAW 246.7 cells). The authors' findings showed that nitric oxide (NO) was significantly inhibited by thalidomide (15%) and its analogues (di-thiothalidomide; 15%, tri-thiothalidomide; 32%). The proinflammatory molecules TNF-alpha (tumor necrosis factor-alpha) and IL-6 were not significantly inhibited. Pretreatment with thalidomide and analogues before activation was not different from simultaneous treatment. Inhibition of inducible nitric oxide synthase (iNOS) may prove to be an important target for the anti-inflammatory and anti-cancer effects of thalidomide and related immunomodulatory drugs (IMiDs).
Park
Eunkyue
E
Department of Developmental Neurobiology, NYS Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USA. parkek@omr.state.ny.us
Levis
William R
WR
Greig
Nigel
N
Jung
Euisun
E
Schuller-Levis
Georgia
G
D000818:Animals; D002478:Cells, Cultured; D015850:Interleukin-6 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis*; D013792:Thalidomide / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D013792:Thalidomide