Effects of a new immunotherapeutic agent (CG5601) on endotoxin-induced uveitis.
CG5601 is a novel immunomodulatory substance showing anti-inflammatory properties comparable to thalidomide. To investigate the anti-inflammatory effects of CG5601 in endotoxin-induced uveitis (EIU) and to evaluate its influence on leukocyte-endothelium interaction, the anterior chamber inflammatory reaction was assessed and intravital fluorescence microscopy was carried out at 2, 4, 8 and 24 h. Lewis rats received an intraperitoneal injection of CG5601 (200 mg/kg b.w.) at the time of lipopolysaccharide injection. At 8 and 24 h, CG5601 inhibited the cell migration and protein concentration in the aqueous humor compared to untreated EIU (p < 0.0001). There was no significant difference between nontreated animals and vehicle controls. The treatment of CG5601 reduced the number of rolling leukocytes. At early time points (2 and 4 h), inhibition of rolling leukocyte flux was significant (p < 0.005). The rise of serum TNF-alpha levels in EIU at 2 h was reduced. CG5601 exerts potent anti-inflammatory effects in EIU.
Porstmann
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AU
Department of Ophthalmology, Charité Campus Virchow, Humboldt-Universität, Berlin, Deutschland. agnes_porstmann@hotmail.com
Zwingenberger
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K
Pleyer
U
U
Baatz
H
H
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001082:Aqueous Humor / Q000378:metabolism; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004731:Endotoxins; D005260:Female; D007093:Imidazoles / Q000627:therapeutic use; D036904:Leukocyte Rolling / Q000187:drug effects; D007962:Leukocytes / Q000187:drug effects; D008070:Lipopolysaccharides / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D013141:Spiro Compounds / Q000627:therapeutic use; D013792:Thalidomide / Q000031:analogs & derivatives / Q000627:therapeutic use; D013844:Thiazoles / Q000627:therapeutic use; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014605:Uveitis / Q000139:chemically induced / Q000188:drug therapy*
D000893:Anti-Inflammatory Agents; C474509:CG5601; D004731:Endotoxins; D007093:Imidazoles; D008070:Lipopolysaccharides; D013141:Spiro Compounds; D013844:Thiazoles; D014409:Tumor Necrosis Factor-alpha; D013792:Thalidomide