title: Preventive and therapeutic anti-inflammatory effects of systemic and topical thalidomide on endotoxin-induced uveitis in rats.
abstract: 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.
authors.affiliation: Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, CEP 88049-900, Florianópolis, SC, Brazil.
authors.forename: Gustavo Büchele
authors.initials: GB
authors.lastname: Rodrigues
authors.forename: Giselle Fazzioni
authors.initials: GF
authors.lastname: Passos
authors.forename: Gabriella
authors.initials: G
authors.lastname: Di Giunta
authors.forename: Cláudia Pinto
authors.initials: CP
authors.lastname: Figueiredo
authors.forename: Eduardo Büchele
authors.initials: EB
authors.lastname: Rodrigues
authors.forename: Astor
authors.initials: A
authors.lastname: Grumman
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Medeiros
authors.forename: João B
authors.initials: JB
authors.lastname: Calixto
mesh_terms: D000284:Administration, Oral; D000287:Administration, Topical; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001082:Aqueous Humor / Q000276:immunology* / Q000378:metabolism; D015153:Blotting, Western / Q000379:methods; D051546:Cyclooxygenase 2; D003907:Dexamethasone / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005136:Eye Proteins / Q000378:metabolism; D007375:Interleukin-1 / Q000276:immunology; D007962:Leukocytes / Q000276:immunology; D008070:Lipopolysaccharides; D008297:Male; D008565:Membrane Proteins; D023421:Models, Animal; D052247:Nitric Oxide Synthase Type II / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013792:Thalidomide / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000276:immunology; D014605:Uveitis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D005136:Eye Proteins; D007375:Interleukin-1; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D014409:Tumor Necrosis Factor-alpha; D013792:Thalidomide; D003907:Dexamethasone; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human