Abstract
Purpose: :
Behçet’s disease (BD) causes a chronic, relapsing refractory uveoretinitis, with inflammatory cell infiltration, mainly composed of neutrophils. Toll like receptor (TLR) 2 and 4 as receptors of endotoxin are expressed on the polymorphonuclear leukocyte (PMNs). In this study, we investigated the expressions of TLR2 and TLR4 on peripheral blood mononuclear cells (PBMC) of BD patients with refractory uveoretinitis before and after treatment with tumor necrosis factor (TNF)-alpha inhibitor, infliximab.
Methods: :
Seven BD patients with refractory uveitis diagnosed at Tokyo Medical University Hospital treated with 5mg/kg of infliximab, enrolled in this study. Any subjects were taking no immunosuppressive drugs except infliximab. Informed consent was obtained from all patients. PBMC was collected before and two weeks after infliximab treatment to analyze TLR 2 and 4 by flow cytometry. In addition, T cells were purified from PBMC using AutoMAX and were analyzed for intracellular cytokine production (IFN-γ, IL-10, IL-17) by flow cytometry.
Results: :
Intraocular inflammation and extraocular symptoms were improved in all BD patients after infliximab. TLR4 expression on PBMC collected from the BD patients with infliximab treatment was reduced in all BD compared to pre-treatment of infliximab. TLR2 expression on PBMC was reduced in 5 of 7 BD patients compared to pre-treatment of infliximab. Intracellular cytokine productions (IFN-γ, IL-10 and IL-17) were not significantly changed before and after infliximab treatment. Infliximab treatment induced an infusion reaction as side effect in one patient.
Conclusions: :
Expressions of TLR on PBMC was reduced in BD treated with infliximab. TLR expressions could be a marker as the efficacy of infliximab treatment.
Keywords: uveitis-clinical/animal model • immunomodulation/immunoregulation • receptors