The efficacy of systemic and intravitreal infliximab treatments in an endotoxin-induced uveitis model

Donmez O., YAMAN A., ÖZTÜRK A. T., AKTAŞ S., ALTUN Z. S., YILMAZ O.

CUTANEOUS AND OCULAR TOXICOLOGY, vol.38, no.4, pp.360-369, 2019 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 38 Issue: 4
  • Publication Date: 2019
  • Doi Number: 10.1080/15569527.2019.1632883
  • Journal Name: CUTANEOUS AND OCULAR TOXICOLOGY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.360-369
  • Keywords: Endotoxin, inflammation, infliximab, intravitreal, uveitis, TUMOR-NECROSIS-FACTOR, HIGH-DOSE INFLIXIMAB, FACTOR-ALPHA, TNF-ALPHA, MACULAR DEGENERATION, MONOCLONAL-ANTIBODY, THERAPY, DISEASE, CORTICOSTEROIDS, INTERLEUKIN-6
  • Dokuz Eylül University Affiliated: Yes

Abstract

Purpose: To compare the efficacy of systemic and intravitreal infliximab treatments in an experimental endotoxin-induced uveitis (EIU) model. Methods: Twenty-eight white New Zealand rabbits were equally divided into 4 groups. Group 1 received an intravitreal injection of 0.1 cc saline, group 2 received an intravitreal injection of 2 mu g/0.1 cc lipopolysaccharide (LPS), group 3 received an intravitreal injection of 2 mu g/0.1 cc LPS and 2 mg/0.1 cc infliximab, and group 4 received intravitreal injection of 2 mu g/0.1 cc LPS and intravenous injection of 5 mg/kg infliximab. Clinical, biochemical (aqueous and vitreous humour protein levels and TNF-alpha concentrations), and histopathological evaluations were performed. Results: The clinical examination score was lower in group 4 than in group 2 (p = 0.006); but there was no significant difference between groups 2 and 3 (Bonferroni correction, p = 0.016). No statistically significant difference was found among groups 2, 3, and 4 for aqueous humour protein levels (p > 0.05). Significantly higher aqueous humour concentrations of TNF-alpha was measured in group 3 comparing to both group 1 and 4 (p = 0.003 and p = 0.002, respectively). No significant difference was found in vitreous protein levels or TNF-alpha concentrations among all study groups (Bonferroni correction, p = 0.026 and p = 0.101, respectively). Histopathological evaluation of the uveal tissue and anterior chamber reaction revealed the highest inflammation in group 3 (p < 0.001). In group 4, histopathological evaluation of uveal tissue was lower than in groups 2 and 3 (p < 0.001 and p = 0.001, respectively); whereas there was no difference in anterior chamber inflammation between groups 2 and 4 (p = 1.00). Conclusion: Intravitreal 2 mg/0.1 cc infliximab injection exacerbated inflammation in an EIU model; whereas systemic infliximab treatment at a dose of 5 mg/kg suppressed inflammation effectively and rapidly.