Preventive and Therapeutic Anti-Inflammatory Effects of Systemic and Topical Thalidomide on Endotoxin-Induced Uveitis in Rats

Abstract

Purpose:: To investigate the actions 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).

Methods:: The effects of thalidomide were evaluated on endotoxin-induced leucocyte and protein infiltration and also on the production of interleukin (IL)-1ß and tumour necrosis factor (TNF)-α 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 the retinal tissue. EIU was produced by a hindpaw injection of lipopolysaccharide (LPS, 200 µg; 24 h prior) 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, thalidomide 5 % was applied topically to both eyes at 6, 12 and 18 hours after LPS administration.

Results:: 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-1ß and TNF-α in the AqH. Similar results were verified 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.

Conclusions:: 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.

Keywords: uveitis-clinical/animal model • immunomodulation/immunoregulation • drug toxicity/drug effects