Analysis of a Functional IL-6 Gene Polymorphism in HLAB27 Associated and Intermediate Uveitis Gives New Insight in Disease Pathogenesis and Commonality with Other Autoimmune Diseases.

PURPOSE: Interleukin 6 (IL-6) plays a crucial role in both adaptive and innate immunity. The rs1800795 gene polymorphism of IL-6 is associated with various autoimmune diseases, like multiple sclerosis. METHODS: 134 patients with HLAB27 positive iridocyclitis, 84 patients with intermediate uveitis, 132 controls, and 65 HLAB27 positive controls were recruited for the present case-control study. Main outcome measures were genotype distribution and allelic frequencies determined by polymerase chain reaction. RESULTS: The frequency of carriers of the minor allele for rs1800795 was significantly higher in patients with intermediate uveitis compared to controls (p = 0.04; OR: 1.46; CI: 1.02-2.11). Frequencies of the minor allele for rs1800795 did not differ significantly in patients with HLAB27 associated uveitis when compared to controls (p > 0.05). CONCLUSION: These findings further deepen our understanding of the commonality between multiple sclerosis and intermediate uveitis. Given the functionality of the investigated polymorphism, new pathophysiological insights are gained that help to evaluate possible therapeutic targets.

Interleukin-6 in the pathogenesis of posterior capsule opacification and the potential role for interleukin-6 inhibition in the future of cataract surgery.

Posterior capsule opacification (PCO) is a debilitating and relatively common complication of cataract surgery despite modern medical and surgical advances. The pathophysiology of this condition has largely been attributed to peptide mediators, such as transforming growth factor-beta (TGFß), epidermal growth factor (EGF) and matrix metalloproteinases (MMPs), with the inhibition of these and other related molecules showing promising results. Studies have also shown that the levels of interleukin-6 are elevated in the eyes following cataract surgery and in various ocular inflammatory disorders that predispose to PCO development. This review proposes, utilizing ocular and extra-ocular disease models, several potential pathways through which IL-6 may modulate the activity of TGFß, EGF, MMP-2/-9 and immune cells to promote PCO. Among the IL-6-mediated pathways discussed are the transactivation of EGF receptor, the up-regulation of TGFß and MMP-2/-9, and the loss of ocular immune privilege through trans-signaling, down-regulation of T-regulatory cells (Tregs) and up-regulation of Th17 cells. After establishing both the potential role of ocular IL-6 in the development of PCO and the apparent upstream activity of IL-6 in relation to the known mediators of PCO, the author hypothesizes that intraoperative anti-IL-6 therapy may be of great benefit in reducing all parameters of PCO pathogenesis. This review also provides a strong basis for carrying out multiple experimental studies with IL-6 inhibitors to further elucidate the specific pathways by which IL-6 may promote PCO as well as to better determine what role inflammation may play in this disease process.