Expression of 12 cytokines in aqueous humour of uveal melanoma before and after combined Ruthenium-106 brachytherapy and transpupillary thermotherapy

Abstract

Purpose: To determine the aqueous humour levels of 12 cytokines in eyes with uveal melanoma and whether their expression changes after combined Ru-106 brachytherapy and transpupillary thermotherapy (TTT).

Methods: Aqueous humour samples were collected from 20 patients with previously untreated uveal melanoma undergoing combined Ru-106 brachytherapy and TTT, both at the time of plaque placement and removal. Using multiplex biochip array technology, 12 different cytokines were measured, including interleukin (IL)-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, vascular endothelial growth factor (VEGF), tumour necrosis factor (TNF)-α, interferon (IFN)-γ, epidermal growth factor (EGF) and monocyte chemoattractant protein (MCP)-1. Aqueous humour from 20 patients undergoing cataract surgery was used as control.

Results: IL-6, IL-8, IFN-γ and MCP-1 were highly expressed in uveal melanoma, whereas IL-2, IL-10 and TNF- α were low in expression. There was a positive correlation between tumour height and IL-8 level (p = 0.020). Vascular endothelial growth factor tends to be highly expressed in melanoma-containing eyes (p = 0.056). Levels of IL-6, IL-8 and IL-1β increased after the mean 117 ± 38 hrs of brachytherapy and adjunctive TTT with a tumour apex dose of 61 ± 28 Gy and a scleral contact dose of 786 ± 226 Gy. Increase in levels of IL-6 (p = 0.003) and IL-8 (p = 0.046) positively correlated with scleral contact dose.

Conclusions: Cytokines such as IL-6, IL-8, IFN-γ and MCP-1 may be implicated in the progression of uveal melanoma. Ocular irradiation from a Ru-106 plaque promoted an increase in the levels of IL-6, IL-8 and IL-1β, modulation of which could be useful in managing radiation-related side effects.