Interleukin-6 blockade in ocular inflammatory diseases

Abstract

SummaryInterleukin-6 (IL-6) is a key cytokine featuring redundancy and pleiotropic activity. It plays a central role in host defence against environmental stress such as infection and injury. Dysregulated, persistent interleukin (IL)-6 production has been implicated in the development of various autoimmune, chronic inflammatory diseases and even cancers. Significant elevation of IL-6 has been found in ocular fluids derived from refractory/chronic uveitis patients. In experimental autoimmune uveitis models with IL-6 knock-out mice, IL-6 has shown to be essential for inducing inflammation. IL-6 blockade can suppress acute T helper type 17 (Th17) responses via its differentiation and, importantly, can ameliorate chronic inflammation. Tocilizumab, a recombinant humanized anti-IL-6 receptor antibody, has been shown to be effective in several autoimmune diseases, including uveitis. Herein, we discuss the basic biology of IL-6 and its role in development of autoimmune conditions, focusing particularly on non-infectious uveitis. It also provides an overview of efficacy and safety of tocilizumab therapy for ocular inflammatory diseases.

The Promise and Limitations of TNF-α Inhibition for Uveitis

“…Others have described similarly beneficial responses to tocilizumab in selected patients with refractory uveitis. [18][19][20][21][22][23] Taken together, these findings support the notion that the use or addition of an anti-TNF-a agent can help achieve control of uveitis in a high proportion of patient with uveitis, particularly those with Behçet's disease and JIA, two conditions for which TNF-a inhibitors are now strongly recommended as standard of care in the step-wise management of ocular inflammation. 24 The studies cited above also highlight, however, some of the limitations of TNF-a inhibitors, including the unpredictably varied response of each TNF-a inhibitor in an individual patient, both initially and over time, and the disappointingly low rate of successful discontinuation.…”

A Novel Biomarker in Diabetic Macular Edema with Serous Retinal Detachment: Serum Chitinase-3-Like Protein 1

“…These cells were reported to be a source of IL-6 [5, 30]. As a potent proinflammatory cytokine, it is a key factor in host defense against environmental stress such as infection, inflammation, and injury [31]. Levels of IL-6 were shown to be increased in the eyes of patients with DR, particularly in proliferative stages of the disease [32, 33].…”

Expression profile of IL-1 family cytokines in aqueous humor and sera of patients with HLA-B27 associated anterior uveitis and idiopathic anterior uveitis

“…Despite intensive clinical and basic research on mechanisms of autoimmune diseases, the underlying molecular and pathogenic mechanisms in these two clinical entities of AAU remain unclear. Autoreactive T cells, from Th1, Th17 and Th2 lineages, are believed to be involved in pathogenesis of uveitis, however blockage of Th1 or Th17 alone might not be sufficient to suppress the inflammation or prevent further attack (Usui, 2007;Yoshimura et al, 2009;Horai and Caspi, 2011;Mesquida et al, 2014).…”