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

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• 作者：Gustavo Bü ; chele Rodrigues ; Giselle Fazzioni Passos ; Gabriella Di Giunta ; Clá ; udia Pinto Figueiredo ; Eduardo Bü ; chele Rodrigues ; Jr. ; Astor Grumman ; Rodrigo Medeiros ; Joã ; o B. Calixto
• 关键词：thalidomide ; uveitis ; tumour necrosis factor-α ; interleukin-1β ; cyclooxygenase-2 ; inducible nitric oxide synthase ; inflammation
• 刊名：Experimental Eye Research
• 出版年：2007
• 出版时间：March 2007
• 年：2007
• 卷：84
• 期：3
• 页码：553-560
• 全文大小：790 K

文摘

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)-1β 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 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-1β and TNF-α 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.