Abstract
PURPOSE. Posterior segment intraocular inflammation (PSII) is a putative Th1 CD4(+) cell mediated autoimmune disorder. In experimental autoimmune uveoretinitis, neutralization of tumor necrosis factor (TNF)-alpha induces suppression of Th1 cells, macrophage activation, and target organ damage. Previous studies implicated an efficacy of anti-TNFalpha therapies in patients with PSII. This study investigated the immunomodulatory effect of anti-TNFa therapy to find predictors of effective immunosuppression in PSII.
METHODS. Fifteen patients with PSII refractory to conventional immunosuppressive therapy received a single infusion of a recombinant protein generated by fusing the p55 TNFalpha receptor. with human IgG1. During 17 treatment periods, visual acuity (logarithm of the minimum angle of resolution [logMAR]) was monitored as a response criterion. Phenotype markers of CD4(+) T cells were analyzed before and 2, 4, and 12 weeks after therapy. Expression of intracellular cytokines (interferon [IFN]-gamma, interleukin [IL]-10, and TNFa) and Th1/Th2-specific chemokine receptors (CXCR3, CCR4, and CCR5) on peripheral blood CD4(+) T cells was determined using flow cytometry.
RESULTS. The fraction of IL-10 -expressing CD4+ T cells was increased during 12 of 17 treatment periods within 2 weeks after treatment. During eight treatment periods, this increase was associated with an improvement of visual acuity of at least 0.2 logMAR within 4 weeks (P = 0.029). The ratio between IL-10- and IFNgamma- expressing CD4+ T cells was significantly increased 2 weeks after therapy (P = 0.015). There was no significant change of CXCR3, CCR4, or CCR5 expression.
CONCLUSIONS. Neutralizing TNFa activity in PSII increases the fraction of peripheral blood CD4(+) T cells expressing IL-10, which correlates with a recovery of visual function.
Original language | English |
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Pages (from-to) | 170-176 |
Number of pages | 6 |
Journal | Investigative Ophthalmology & Visual Science |
Volume | 45 |
Issue number | 1 |
DOIs | |
Publication status | Published - 2004 |
Keywords
- EXPERIMENTAL AUTOIMMUNE UVEORETINITIS
- NECROSIS-FACTOR-ALPHA
- CHEMOKINE RECEPTOR EXPRESSION
- RHEUMATOID-ARTHRITIS
- CHEMOTACTIC RESPONSIVENESS
- OCULAR INFLAMMATION
- BEHCETS-DISEASE
- UVEITIS
- CYTOKINES
- INHIBITION
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Iain Fraser Cytometry Centre
Andrea Holme (Manager), Linda Duncan (Senior Application Scientist), Ailsa Laird (Technician) & Kate Burgoyne (Technician)
Institute of Medical SciencesResearch Facilities: Facility