AB0176 increased toll-like receptor 5 signalling and IL-6 production in monocytes from patients with systemic lupus erythematosus

Background The innate immune system contributes to the pathogenesis of SLE, in part through the activity of Toll-like receptors (TLRs), a family of pattern-recognition receptors. Nucleic acid containing immune-complexes, which are characteristic of SLE, activate the RNA and DNA sensing TLRs 7 and 9, resulting in interferon production [1]. Although a role for interferon is well established in SLE, other cytokines such as interleukin (IL)-6 have also been shown to correlate with disease activity, with an anti-IL-6 receptor antibody (Tocilizumab) demonstrating some early success in clinical trials [2][3]. Objectives TLR-7 and 9 are primarily considered drivers of IFN production, but in this study, our aim was to explore the biology of other key TLR's (4, 5 and 8) in SLE in vitro, specifically the role of these TLR's in the induction of interleukin-6 production by monocytes. Methods Freshly-obtained peripheral blood monocytes from patients with known SLE (satisfying standard diagnostic and seroplogical criteria) were studied, contemporaneously with cells from healthy volunteers. TLR expression was evaluated by flow cytometry. Monocyte IL-6 production was measured by ELISA, and evaluation of mRNA levels, before and after in vitro stimulation with flagellin. Results An increase in TLR5 expression (p