Thalidomide inhibits leukocyte-endothelium interaction in endotoxin-induced uveitis

Ophthalmic Res. Sep-Oct 2001;33(5):256-63. doi: 10.1159/000055678.

Abstract

To investigate the effects of thalidomide on leukocyte-endothelium interaction in iris vessels of rats with an endotoxin-induced uveitis (EIU), intravital fluorescence microscopy was used to quantify leukocyte adhesion to the vascular endothelium of iris venules in Lewis rats at 2, 4, 8 and 24 h after induction of EIU. Animals (n = 84) received a single intraperitoneal dose of either thalidomide (80 mg/kg body weight) or prednisolone (10 mg/kg body weight). Both drugs significantly reduced firm adhesion of leukocytes at 4, 8 and 24 h. Thalidomide caused earlier suppression of leukocyte rolling than prednisolone (4 vs. 8 h). TNF-alpha plasma levels peaked at 2 h and were not significantly reduced in any group compared with controls. Cell count and protein concentration in aqueous humor were significantly reduced by prednisolone and thalidomide at 24 h (p < 0.05). Thalidomide exerts its anti-inflammatory effects by an inhibition of leukocyte-endothelium interaction. Compared with prednisolone, thalidomide shows earlier inhibition of leukocyte rolling, indicating modulation of adhesion molecule expression and/or function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Adhesion / drug effects
  • Endothelium, Vascular / drug effects*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Glucocorticoids / pharmacology
  • Immunosuppressive Agents / pharmacology*
  • Iris / blood supply
  • Leukocyte Count
  • Leukocytes / drug effects*
  • Lipopolysaccharides
  • Microscopy, Fluorescence
  • Prednisolone / pharmacology
  • Rats
  • Rats, Inbred Lew
  • Salmonella typhimurium
  • Thalidomide / pharmacology*
  • Tumor Necrosis Factor-alpha / metabolism
  • Uveitis, Anterior / chemically induced
  • Uveitis, Anterior / prevention & control*

Substances

  • Glucocorticoids
  • Immunosuppressive Agents
  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha
  • Thalidomide
  • Prednisolone