Abstract

Therapeutically controlling inflammation is essential for the clinical management of many high-prevalence human diseases. Drugs that block the pro-inflammatory cytokines tumour-necrosis factor- and interleukin-1 (IL-1) can improve outcomes for rheumatoid arthritis and other inflammatory diseases but many patients remain refractory to treatment. Here we explore the need for developing new types of anti-inflammatory drugs and the emergence of novel drug targets based on the clustering of IL-1 receptors into multi-protein aggregates associated with cell adhesions. Interference with receptor aggregation into multi-protein complexes effectively abrogates IL-1 signalling. The exploration of the crucial molecules required for receptor clustering, and therefore signal transduction, offers new targets and scope for anti-inflammatory drug development.

Author affiliations

1. CIHR Group in Matrix Dynamics, University of Toronto, Toronto, Canada M5S 3E2.
2. Toronto General Hospital Research Institute of the University Health Network, and Division of Respirology, Department of Medicine, University of Toronto, Toronto, Canada M5G 2C4.
3. Department of Medicine, University of Manitoba, Winnipeg, Canada.

Correspondence to: Christopher. A. McCulloch¹ Email: christopher.mcculloch@utoronto.ca

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