Etanercept treatment in the endotoxin-induced uveitis of rats.
This study was conducted to investigate therapeutic value of a soluble tumor necrosis factor-alpha (TNF-alpha) receptor, etanercept, in a rat model of endotoxin-induced uveitis (EIU). Forty-two inbred male Lewis rats were divided into seven equal groups. 200 microg of Escherichia coli 055:B55 lipopolysaccharide (LPS) was injected in one hind footpad of the Groups 2, 3, 4, 5, 6, and 7 rats. Group 5, 6, and 7 rats also received subcutaneous etanercept 24 hr prior to LPS injection at a dose of 0.4 mg kg(-1). Group 1 rats were used as controls. Eight, 24, and 48 hr after treatment clinical uveitis scores (miosis, iris hyperemia, and hypopyon) were assessed by a masked observer and the rats were euthanized. Neutrophil leukocytes, CD8+, CD4+, and CD45RO+ cells in the anterior uveal tissue were counted either after hematoxylin-eosin or monoclonal antibody staining. TNF-alpha levels were also measured in the aqueous humor samples by an ELISA method. Etanercept treatment significantly improved clinical uveitis scores at all examination points compared to the LPS injected animals. The improvement was almost complete expect for the miosis score, since no significant difference was detected between the controls and LPS + Etanercept treated animals at all examination points. Cell counts were also at significantly lower levels in LPS + Etanercept treated animals at all examination points, except for CD8+ and CD45RO+ cell counts at 24 hr examination point. There was no significant difference between the controls and LPS + Etanercept treated animals at all examination points as with CD4+ and CD45RO+ cell counts at 48 hr. Our data showed that etanercept had a definite effect on the treatment of EIU. Further studies should clarify its efficacy on clinical uveitis conditions.
Avunduk
Mustafa Cihat
MC
Department of Pathology, School of Medicine, Selcuk University, Konya, Turkey.
Avunduk
Avni Murat
AM
Oztekin
Esma
E
Baltaci
Abdülkerim Kasim
AK
Ozyazgan
Yilmaz
Y
Mogolkoc
Rasim
R
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D002924:Ciliary Body / Q000276:immunology; D004195:Disease Models, Animal; D000068800:Etanercept; D007074:Immunoglobulin G / Q000627:therapeutic use*; D007150:Immunohistochemistry / Q000379:methods; D007498:Iris / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000187:drug effects; D007958:Leukocyte Count; D008070:Lipopolysaccharides; D008297:Male; D015877:Miosis / Q000188:drug therapy; D009504:Neutrophils / Q000187:drug effects; D051381:Rats; D011917:Rats, Inbred Lew; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D014605:Uveitis / Q000188:drug therapy*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; C482199:lipopolysaccharide, E coli O55-B5; D017493:Leukocyte Common Antigens; D000068800:Etanercept