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The Role of Soluble TNF Receptors for TNF- in Uveitis

¹From the Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University Graduate School of Medicine, Tokyo, Japan; and the ²Department of Ophthalmology, Kurume University School of Medicine, Fukuoka, Japan.

PURPOSE. To investigate the presence of soluble tumor necrosis factor receptors (sTNF-Rs) and TNF- in the ocular fluids of patients with uveitis and the capacity of sTNF-Rs to affect TNF- production by intraocular T cells.

METHODS. Ocular fluid samples were collected from patients with active and inactive uveitis, as well as from control subjects without uveitis. The sTNF-Rs and TNF- levels were measured by enzyme-linked immunosorbent assay (ELISA). T-cell clones (TCCs) were established from intraocular infiltrating cells, and the TCCs were cocultured with recombinant sTNF-Rs or TNF-. The supernatants were measured by ELISA. The neutralization of sTNF-R production by TCCs was evaluated with an anti-human TNF-R antibody.

RESULTS. Significantly higher amounts of sTNF-R1 and -R2 were present in the ocular fluids of patients with active uveitis than in the ocular fluids of those with inactive uveitis and in control subjects. Significantly higher amounts of TNF- were present in the ocular fluids of patients with active uveitis than in those with inactive uveitis. Recombinant sTNF-Rs enhanced TNF- production by TCCs in a dose-dependent manner. Similarly, recombinant TNF- enhanced sTNF-Rs production by the TCCs, and production was neutralized with anti-human TNF-R antibody.

CONCLUSIONS. sTNF-Rs are present in the ocular fluids of patients with uveitis. Intraocular levels of sTNF-Rs are significantly increased in patients with uveitis, particularly in those with active uveitis. The data suggest that intraocular sTNF-Rs may play a regulatory role in ocular inflammation such as occurs in uveitis.

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