title: Systemic administration of an anti-tumor necrosis factor-alpha monoclonal antibody protects against endotoxin-induced uveitis in rats.
abstract: OBJECTIVE
  This study was to evaluate the effect of systemic injection of an anti-tumor necrosis factor alpha (TNF-α) monoclonal antibody (mAb) on endotoxin-induced uveitis (EIU).
  
  
  METHODS
  Fifty-six male Wistar rats (6-8 weeks old) were randomly divided into three groups: EIU, anti-TNF-α mAb + EIU, and control. EIU was induced by injecting Escherichia coli O55:B5 lipopolysaccharide (LPS) into the hind footpad of the rats (150 μg/rat). The anti-TNF-α mAb (1 μg/kg) was administrated 30 min before LPS injection through one-time intravenous injection. The onset time and peak time of EIU were recorded. The serum and aqueous humor (AH) TNF-α, interleukin (IL)-6, and IL-10 levels were measured by ELISA at 4, 24, and 72 h post-LPS injection. Clinical manifestations of EIU and eye histopathology were scored.
  
  
  RESULTS
  Compared with the EIU rats, anti-TNF-α mAb + EIU rats showed significantly delayed onset of uveitis (t = 7.41, P< 0.001), lower clinical scores and histopathological grades (t = 3.18/2.22, P< 0.001), reduced levels of TNF-α (F = 15.06/59.43, P< 0.001) and IL-6 (F = 99.63/14.92, P< 0.001), and increased levels of IL-10 (F = 24.94/8.99, P< 0.001) in the serum and AH. AH TNF-α, serum IL-6, and AH IL-6 levels are positively correlated, whereas serum IL-10 levels were negatively correlated with EIU activity.
  
  
  CONCLUSIONS
  Antagonizing TNF-α by system injection of the anti-TNF-α mAb protects against EIU in rats. Blocking TNF-α signaling could be a useful strategy for managing uveitis.
authors.affiliation: Department of Ophthalmology, The Eye Hospital Affiliated of Shandong Medical College, Linyi, China.
authors.forename: Qingman
authors.initials: Q
authors.lastname: Ge
authors.affiliation: Department of Endocrinology, The Third Central Hospital of Tianjin, Tianjin, China.
authors.forename: Shaocheng
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology, Tianjin Eye Hospital, Tianjin, China.
authors.forename: Yuezhong
authors.initials: Y
authors.lastname: Zheng
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D001082:Aqueous Humor / Q000378:metabolism*; D004195:Disease Models, Animal; D004731:Endotoxins / Q000633:toxicity; D004797:Enzyme-Linked Immunosorbent Assay; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology* / Q000378:metabolism; D014606:Uveitis, Anterior / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D004731:Endotoxins; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10