The role of tumour necrosis factor (TNF-alpha) in experimental autoimmune uveoretinitis (EAU).

Department of Clinical Sciences at South Bristol, University of Bristol, Bristol Eye Hospital, Lower Maudlin Street, Bristol BS1 2LX, UK.
Progress in Retinal and Eye Research (Impact Factor: 9.9). 12/2004; 23(6):617-37. DOI: 10.1016/j.preteyeres.2004.06.005
Source: PubMed

ABSTRACT The pleiotropic cytokine tumour necrosis factor-alpha (TNF-alpha) is released from cells that include macrophages and T-cells during inflammatory responses, orchestrating the initiation of further leucocytic infiltration via adhesion molecule upregulation, dendritic cell maturation and survival, macrophage activation and driving Th1 T-cells responses within tissues. Exposure to TNF also plays a role in maintaining tissue homeostasis, particularly relating to resident cell responses of both microglia and retinal pigment epithelium. Depending on the balance between duration and dose of TNF exposure, an environment where full expression of inflammatory and autoimmune responses within tissues may occur. In experimental autoimmune uveoretinitis (EAU), increased tissue concentrations of TNF facilitate the on-going T-cell effector responses and macrophage activation. These are responsible for targeted and bystander tissue damage and can be suppressed by anti-TNF therapies, in particular, those directed at the p55 TNF receptor. The ability to suppress disease experimentally has led to the successful translation of anti-TNF therapy for treatment of uveitis in cohort studies and phase I/II trials where, additionally, altered peripheral blood CD4(+) T-cell profiles can be demonstrated following each treatment.

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