Increased soluble interleukin-6 receptor in vitreous fluid of proliferative vitreoretinopathy

Purpose. To clarify the effect of the interaction between interleukin-6 (IL-6) and its soluble receptor (sIL-6R) on retinal pigment epithelial (RPE) cell proliferation in proliferative vitreoretinopathy (PVR). Methods. Concentrations of IL-6 and sIL-6R molecules in vitreous fluids were measured in eyes with PVR and idiopathic macular hole (MH), and the localization of IL-6 and IL-6R on the PVR fibrous membrane was studied. Production of IL-6 and sIL-6R by cultured RPE cells and the effect of the IL-6/sIL-6R complex on growth of cultured RPE cells were analyzed. Results. Positive staining of IL-6 and IL-6R was observed in proliferating membranes in all PVR cases. IL-6 and sIL-6R concentrations in vitreous fluid from eyes with PVR were significantly higher than in eyes with MH (p < 0.05). A time-dependent increase in IL-6 molecules was identified in the culture medium of RPE cells, although sIL-6R was not detected. Dose-dependent growth of RPE cells was observed in the three concentrations (50, 100, and 500 ng/ml) of sIL-6R used. Conclusions. IL-6 derived from blood during the breakdown of the blood-retinal barrier (BRB) and produced by RPE cells and hematogenous sIL-6R cause RPE proliferation.