Implications
In 2013, Schett et al. published a prescient review in Nature Medicine, noting the startling success of targeted cytokine inhibitors in the 1990s “indicates that chronic inflammatory diseases depend on fragile communication networks of cytokines, which collapse upon neutralization of functionally vulnerable nodes, such as TNFα.”2
Indeed, rheumatologists now think in terms of cytokine networks on a daily basis. You say gout? We think IL-1. Psoriatic arthritis? TNFα, IL-17, IL-12/23 and Janus kinase immediately come to mind. What about IBD-arthritis? Same list, omitting IL-17. Cytokine networks are becoming so second nature to rheumatologists that we can’t help but dream of a day when we can drop broad immunosuppressants almost entirely. (We’re looking at you, GUSTO [giant cell arteritis treatment with ultra-short glucocorticoid and tocilizumab].3)
With this background in mind, the base article for this team advances our understanding of cytokines by studying the cytokine profiles of four different rheumatic diseases all at once, ultimately describing a shared cytokine network particularly active in patients with severe disease. Besides the obvious implications for future drug development, this study raises an interesting question for current and future researchers: What other cytokine networks are waiting to be described if the same methodology is applied to other groups of rheumatic diseases? If you could choose another group of four conditions to put into this cytokine network detangler machine, what would they be? Will studies using the methodology in PRECISESADS eventually allow us to redefine rheumatic diseases by shared and unique pathophysiology rather than clinical manifestations alone?
Chances in the Tournament
In our view, this team’s chances in the tournament depend on how narrowly or broadly the Blue Ribbon Panel views the concept of cytokine networks in rheumatology. The base article for this team uses a complex, sophisticated playbook to describe a shared pro-inflammatory cytokine network in four rheumatic conditions. Although this fact will certainly score some points with the panel, it may not be enough for the team to escape its first-round matchup against the upstart anti-NET antibodies. However, the panel may apply the concept of cytokine networks more broadly, viewing the base article as a crucial piece in the massive cytokine jigsaw puzzle that is continually revolutionizing our understanding of disease pathogenesis and therapeutic targets in rheumatology. If that’s the case, this team may be cutting down the nets at the end of the tournament. Surrounded, of course, by a cloud of cytokine confetti.
