Comparison of acute effect of systemic versus intravitreal infliximab treatment in an experimental model of endotoxin-induced uveitis

J Ocul Pharmacol Ther. 2014 Feb;30(1):74-80. doi: 10.1089/jop.2012.0238. Epub 2013 Oct 11.

Abstract

Purpose: In this study, we investigated the efficacy of systemic and intravitreal (IV) infliximab treatments and compared these 2 different treatment modalities in an experimental model of endotoxin-induced uveitis (EIU).

Methods: Twenty-four white New Zealand rabbits were equally divided into 4 groups. Group 1 received IV injection of lipopolysaccharide (LPS), group 2 received IV injections of LPS and saline, group 3 received IV LPS and IV 2 mg/0.1 cc infliximab, and group 4 received IV LPS and 5 mg/kg intravenous infliximab. Inflammation was determined with objective and subjective tests. The subjective test was clinical determination of uveitis, the objective tests were determination of protein concentrations and tumor necrosis factor alpha (TNF-α) levels and histopathology.

Results: Clinical examination score was lower in group 3 and group 4 (4±0.6 and 3.5±1.6, respectively) when compared with group 1 (P=0.02; P=0.04, respectively) and group 2. In group 3 and 4, the aqueous and vitreous protein and TNF-α concentration measured significantly lower than group 1 and 2. In histopathologic examination, there was no statistically significant difference between group 1, 2, and 3 (3.5±0.5, 3.6±0.5, 3.6±0.5, respectively). However, the lowest histopathologic inflammation was determined in group 4 (2.5±0.5) (compared with group 1 and group 3, respectively; P=0.03; P=0.014).

Conclusion: In a rabbit model of experimental EIU, intravenous administration of infliximab was more effective than IV route in an acute period.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage*
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / pharmacology
  • Disease Models, Animal
  • Eye Proteins / metabolism
  • Infliximab
  • Injections, Intravenous
  • Intravitreal Injections
  • Lipopolysaccharides / toxicity
  • Rabbits
  • Tumor Necrosis Factor-alpha / metabolism*
  • Uveitis / drug therapy*
  • Uveitis / pathology
  • Vitreous Body / metabolism

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Antibodies, Monoclonal
  • Eye Proteins
  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha
  • Infliximab