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AU Porstmann, K Zwingenberger, U Pleyer, C Hartmann, H Baatz; Effects of a Potential New Immunotherapeutic (CG5601) on Endotoxin-induced Uveitis . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3975.
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Purpose: To investigate the anti-inflammatory effects of CG5601 and to evaluate its influence on leukocyte-endothelium interaction. Methods: Uveitis was induced in Lewis rats by i.p. injection of lipopolysaccharide (650µg LPS/kg body weight). CG5601 has immunomodulatory properties comparable to those of thalidomide. 200mg/kg b.w. were administered i.p. simultaneously with the LPS injection. At 2h, 4h, 8h, and 24h after LPS injection, intravital fluorescence microscopy was performed to evaluate leukocyte-endothelium interaction. Rhodamine 6G was used to stain circulating leukocytes. Nontreated rats and rats that received the empty vehicle (carboxymethylcelluloses) served as controls. Each group consisted of 6 animals. Inflammation was evaluated by cell count and by determining protein concentration in the aqueous humor. Serum-TNFα was measured by ELISA. Results: At 8h and 24h, CG 5601 significantly (p<0.0001) inhibited inflammation in the anterior chamber. The cell count in the aqueous humor was 17.8±2.7cells/µl 8h after treatment compared with 73.8±23.5/µl in untreated EIU. The protein concentration was reduced more than half to 2.1±0.5mg/ml compared to the non-treated controls (5.4±0.6 mg/ml). There was no significant difference between non-treated animals and vehicle controls. Treatment of CG 5601 reduced the number of rolling leukocytes. At early time points (2h and 4h) inhibition of the rolling leukocyte flux was significant (p<0.005). The rise of serum-TNFα levels in EIU at 2h was reduced by 70% compared with controls (p<0.002). Conclusion: CG5601 exerts potent anti-inflammatory effects in endotoxin-induced uveitis.
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