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P<P, published online ahead of print May 9, 2008
(Investigative Ophthalmology and Visual Science. )
© 2008 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.08-1953
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Article

Soluble gp130, an antagonist of IL-6 trans-signaling, is elevated in uveitis aqueous humor

Diana Simon 1, Alastair K.O. Denniston 1, Paul J Tomlins 2, Graham R Wallace 1, Saaeha Rauz 3, Mike Salmon 4, Philip I. Murray 2, and S. John Curnow 1*

1 Medical School, The University of Birmingham, Institute of Biomedical Research, Division of Immunity and Infection, Birmingham, United Kingdom; University of Birmingham, Birmingham and Midland Eye Centre, Academic Unit of Ophthalmology, Division of Immunity and Infection, Birmingham, United Kingdom
2 University of Birmingham, Birmingham and Midland Eye Centre, Academic Unit of Ophthalmology, Division of Immunity and Infection, Birmingham, United Kingdom
3 University of Birmingham, Birmingham and Midland Eye Centre, Academic Unit of Ophthalmology, Division of Immunity and Infection, Birmingham, United Kingdom; Medical School, The University of Birmingham, Institute of Biomedical Research, Division of Immunity and Infection, Birmingham, United Kingdom
4 Medical School, The University of Birmingham, Institute of Biomedical Research, Division of Immunity and Infection, Birmingham, United Kingdom

* To whom correspondence should be addressed. E-mail: s.j.curnow{at}bham.ac.uk.


  Abstract

PURPOSE. To determine the concentrations of soluble gp130, a natural antagonist of IL-6 trans-signaling, in the serum and aqueous humor (AqH) of patients with uveitis. METHODS. Serum was obtained from the peripheral blood of patients with active uveitis and healthy controls. AqH samples were collected from patients with active uveitis and patients without uveitis undergoing routine cataract surgery. Samples were centrifuged and the cell-free supernatant frozen at -80°C. Concentrations of sgp130, sIL-6R and IL-6 were determined by a sandwich ELISA or multiplex bead immunoassay, using standard curves of known concentrations of recombinant cytokines. RESULTS. Serum concentrations of sgp130 were not significantly different between control individuals and patients with active anterior uveitis, regardless of the degree of intraocular inflammation cells. By contrast, the concentration of sgp130 in AqH was very low in patients with no or little inflammation, but increased significantly with disease severity. The greatest elevations of AqH sgp130 were found in patients with the highest cellular activity. Simultaneous measurement of IL-6, sIL-6R and sgp130 revealed a high degree of correlation between the levels of these molecules, especially for sIL-6R and sgp130. CONCLUSIONS. Soluble gp130 is increased in the AqH of patients with active uveitis. It is likely that sgp130 partially inhibits the process of IL-6 trans-signalling during inflammation. However, the concentration found is still far below that in serum, suggesting that increasing the level of sgp130 further may assist in reducing the inflammatory changes induced by IL-6 trans-signalling.

Key Words: uveitis, aqueous humor, cytokine, immunoregulation






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