Preventive and therapeutic anti-inflammatory effects of systemic and topical thalidomide on endotoxin-induced uveitis in rats

Exp Eye Res. 2007 Mar;84(3):553-60. doi: 10.1016/j.exer.2006.11.009. Epub 2007 Jan 12.


The present study examined the outcomes of systemic or topical treatment with thalidomide, a compound that possesses anti-inflammatory, immunomodulatory and anti-angiogenic properties, in rats subjected to endotoxin-induced uveitis (EIU). The effects of thalidomide were evaluated on endotoxin-induced leucocyte and protein infiltration and also on the production of interleukin (IL)-1beta and tumour necrosis factor (TNF)-alpha in rat aqueous humour (AqH). Moreover, the actions of thalidomide were assessed on the cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) protein expression in retinal tissue. EIU was produced by a hindpaw injection of lipopolysaccharide (LPS), in male Wistar rats. Thalidomide (5, 25 and 50 mg/kg) was administered orally 1 h before LPS injection. In another set of experiments, to evaluate the therapeutic efficacy, 5% thalidomide was applied topically to both eyes at 6, 12 and 18 h after LPS administration. The oral pre-treatment with thalidomide decreased, in a dose-dependent manner, the number of inflammatory cells, the protein concentration, and the levels of IL-1beta and TNF-alpha in the AqH. Similar results were found in the AqH of rats that received a topical application of thalidomide. Furthermore, oral (50 mg/kg) and local (5%) thalidomide treatment also reduced expression of the pro-inflammatory proteins COX-2 and iNOS in the posterior segment of the eye. Thalidomide exhibited marked preventive and curative ocular effects in EIU in rats, a property that might be associated with its ability to inhibit the production of inflammatory cytokines and the expression of COX-2 and iNOS. This assembly of data provides additional molecular and functional insights into beneficial effects of thalidomide as an agent for the management of ocular inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Administration, Topical
  • Animals
  • Anti-Inflammatory Agents / therapeutic use*
  • Aqueous Humor / immunology*
  • Aqueous Humor / metabolism
  • Blotting, Western / methods
  • Cyclooxygenase 2
  • Dexamethasone / therapeutic use
  • Dose-Response Relationship, Drug
  • Eye Proteins / metabolism
  • Interleukin-1 / immunology
  • Leukocytes / immunology
  • Lipopolysaccharides
  • Male
  • Membrane Proteins
  • Models, Animal
  • Nitric Oxide Synthase Type II / analysis
  • Nitric Oxide Synthase Type II / metabolism
  • Rats
  • Rats, Wistar
  • Thalidomide / therapeutic use*
  • Tumor Necrosis Factor-alpha / analysis
  • Tumor Necrosis Factor-alpha / immunology
  • Uveitis / drug therapy*
  • Uveitis / immunology
  • Uveitis / metabolism


  • Anti-Inflammatory Agents
  • Eye Proteins
  • Interleukin-1
  • Lipopolysaccharides
  • Membrane Proteins
  • Tumor Necrosis Factor-alpha
  • Thalidomide
  • Dexamethasone
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2
  • PTGS2 protein, human