Increased Levels of Soluble Gp130 in Uveitis Aqueous Humour

Abstract

Purpose:: We have previously shown that IL-6 trans-signalling inhibits apoptosis of aqueous humour T cells during episodes of active uveitis. IL-6 trans-signals are delivered by the cell surface molecule gp130 following binding of the soluble IL-6R/IL-6 complex. As well as being expressed on the surface of many cells, gp130 has been found at high levels in the serum as a soluble molecule (sgp130). This soluble molecule has the capacity to inhibit trans-, but not direct, IL-6 signalling. We aimed to determine the serum and aqueous humour concentrations of sgp130 in patients with uveitis.

Methods:: Serum was obtained from peripheral blood of patients with active uveitis and healthy controls. Aqueous humour (AqH) samples were collected from patients with active uveitis and patients undergoing routine cataract surgery. Samples were centrifuged and the cell-free supernatant frozen at -80ºC. Concentrations of sgp130 were determined by a sandwich ELISA using a standard curve of known concentrations of recombinant cytokine.

Results:: Serum concentrations of sgp130 were not significantly different between uveitis patients and controls (median values 233.4 ng/ml vs 274.7ng/ml; p>0.05). Within the uveitis group there was no association between serum sgp130 levels and disease severity, treatment, classification or underlying aetiology. The concentration of sgp130 in AqH was very low in patients with no or little inflammation but increased significantly with disease severity (median values 8.8ng/ml and 31.5ng/ml for 2+ and 3+ AqH cells, respectively; p<0.05). However, the concentration in AqH was still below that found in serum.

Conclusions:: Soluble gp130 is increased in the AqH of patients with active uveitis, possibly due to breakdown of the blood-aqueous barrier and influx from the serum. 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 may assist in further reducing the inflammatory changes induced by IL-6 trans-signalling.

Keywords: immunomodulation/immunoregulation • uveitis-clinical/animal model • cytokines/chemokines