Role of interleukin-1b in the pathogenesis of diabetic retinopathy

Aim: To examine the role of cytokine interleukin-1b (IL-1b) in retinal capillary cell death in diabetes. Methods: The effect of glucose on the expression of IL-1b was measured in the bovine retinal endothelial cells. The role of IL-1b in the accelerated endothelial cell loss was determined by investigating the effect of human recombinant IL-1b on their apoptosis in normal and high glucose conditions, and was confirmed using interleukin-1 receptor antagonist (IL-1ra). Results: High glucose increased IL-1b expression by 60% compared with cells incubated in 5 mM glucose (p,0.05). Incubation of cells with IL-1b increased NO levels by about 80% and activated NF-kB by 40%. In the same cells apoptosis was increased by 70% and caspase-3 activity was increased by 40%. Supplementation of IL-1b in 20 mM glucose medium further increased nitric oxide and NF-kB, and accelerated apoptosis, and addition of IL-1ra significantly decreased glucose induced abnormalities and apoptosis. Conclusions: IL-1b accelerates apoptosis of retinal capillary cells via activation of NF-kB, and the process is exacerbated in high glucose conditions. These studies suggest a possible role of IL-1b in the development of retinopathy in diabetes, and offer a possible rationale to test IL-1b receptor antagonists to inhibit the development of diabetic retinopathy.