You are here

Article Text

Article menu
Download PDFPDF
New targets
New strategies to control inflammatory synovitis: interleukin 15 and beyond
  1. I B McInnes,
  2. J A Gracie,
  3. M Harnett,
  4. W Harnett,
  5. F Y Liew
  1. Centre for Rheumatic Diseases, Division of Immunology, Infection and Inflammation, University of Glasgow, UK
  1. Correspondence to:
    Dr I B McInnes, Centre for Rheumatic Diseases, University Department of Medicine, Level 3, Queen Elizabeth Building, Glasgow Royal Infirmary, 10, Alexandra Parade, Glasgow G31 2ER, Scotland, UK;
    i.b.mcinnes{at}clinmed.gla.ac.uk

https://doi.org/10.1136/ard.62.suppl_2.ii51

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    STRATEGIES TO TARGET SYNOVITIS

    A broad range of strategies to target inflammatory synovitis is currently being explored. Most approaches require the identification of a single molecule/pathway that is tractable to modulation in the clinic. In general, molecular activities with relevant biological effects are sought within the appropriate target lesion—namely, the synovium. Thereafter, such an activity may be targeted in rodent models of arthritis and the effects on inflammation and articular destruction measured. A moiety with plausible biology and bioactivity in model systems may then move to phase I “proof of concept” studies and thereafter to clinical development (fig 1). The successful targeting of tumour necrosis factor α (TNFα) represents an example of such an approach whereby an effective therapeutic agent has been derived.1,2 However, even after TNF blockade, unmet clinical need clearly persists in inflammatory arthritis. Major challenges remain, in particular the identification of therapeutic responders a priori, and the rational choice of additional targets, either as independent primary therapeutic targets or as synergistic biological targets for future combination applications. This short review will test interleukin 15 (IL15) in this model of new biological development to evaluate its therapeutic potential. Thereafter, an alternative approach will be considered for comparative purposes, whereby a model in which multiple pathways within the synovium are targeted simultaneously using a strategy borrowed from the host-parasite relationship arising from evolutionary pressures over millennia (fig 1).

    Figure 1

    Alternative model approaches, resulting in “proof of concept” clinical studies to target synovitis.

    INTERLEUKIN 15 AS A THERAPEUTIC TARGET

    Our group has recently sought mechanisms whereby innate and acquired immune responses interact during chronic inflammation, with particular emphasis on cytokine biology. Many cytokines present within the synovium derive from macrophages and synovial fibroblasts.3 IL15, a cytokine with structural similarities to IL2,4 is produced primarily by macrophages and as such attracted our attention at an early stage as …

    View Full Text