The role of soluble TNF receptors for TNF-alpha in uveitis.
OBJECTIVE
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.
Sugita
Sunao
S
Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University Graduate School of Medicine, Yushima, Tokyo, Japan. sunaoph@tmd.ac.jp
Takase
Hiroshi
H
Taguchi
Chikako
C
Mochizuki
Manabu
M
D001082:Aqueous Humor / Q000378:metabolism*; D002460:Cell Line; D018920:Coculture Techniques; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism* / Q000494:pharmacology; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000378:metabolism* / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology; D014605:Uveitis / Q000378:metabolism*; D014822:Vitreous Body / Q000378:metabolism*
D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha