Thalidomide inhibits leukocyte-endothelium interaction in endotoxin-induced uveitis.
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.
Baatz
H
H
Department of Ophthalmology, Johann Wolfgang Goethe University, Frankfurt/Main, Germany. holger_baatz@hotmail.com
Tönessen
B
B
Prada
J
J
Pleyer
U
U
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007498:Iris / Q000098:blood supply; D007958:Leukocyte Count; D007962:Leukocytes / Q000187:drug effects*; D008070:Lipopolysaccharides; D008856:Microscopy, Fluorescence; D011239:Prednisolone / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D012486:Salmonella typhimurium; D013792:Thalidomide / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014606:Uveitis, Anterior / Q000139:chemically induced / Q000517:prevention & control*
D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D013792:Thalidomide; D011239:Prednisolone