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(Investigative Ophthalmology and Visual Science. 2007;48:3246-3252.)
© 2007 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.06-1444
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The Role of Soluble TNF Receptors for TNF-{alpha} in Uveitis

Sunao Sugita,1 Hiroshi Takase,1 Chikako Taguchi,2 and Manabu Mochizuki1

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-{alpha} in the ocular fluids of patients with uveitis and the capacity of sTNF-Rs to affect TNF-{alpha} 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-{alpha} 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-{alpha}. 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-{alpha} were present in the ocular fluids of patients with active uveitis than in those with inactive uveitis. Recombinant sTNF-Rs enhanced TNF-{alpha} production by TCCs in a dose-dependent manner. Similarly, recombinant TNF-{alpha} 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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