Cytokines and the Future of Rheumatology

In part 1 of the RheuMuseum video series, Professor Iain McInnes of the University of Glasgow discusses how advances in molecular medicine have revolutionized the treatment of axial spondyloarthritis.

Iain McInnes is vice principal and head of the college of medical, veterinary, and life sciences at the University of Glasgow, Scotland.

TRANSCRIPT:

So rheumatology, let's start at the very beginning, is probably the medical discipline which has advanced most in the last 2 decades. I personally consider it to be at the very forefront of the molecular medicine revolution that has occurred. We are currently doing brain MRI studies before and after we give immune-targeted interventions. And looking at what happens in the brain to people with arthritis. And as we begin to understand how the brain and neuro pathways map in people with chronic pain, fatigue, and so-called cognitive dysfunction—to cut a very long story short, huge things are happening.

This is a particularly important time for us to be thinking about the underlying factors, the background factors, if you like, that we believe lead to the axSpA syndrome. It's almost 50 years since the association between HLA-B27 and axSpA was recognized. And curiously, after half a century of investigation, we're still not absolutely certain how that genetic association works at a mechanistic, functional level. Cytokines could be considered the hormones of the immune system. They are molecular connectors. They allow the immune system to communicate one cell with the other, but also the immune system to communicate with target tissue.

Cytokines have been known about for many decades. The classic is TNF, probably a misnomer, tumor necrosis factor. It's actually a general proinflammatory effector cytokine. It activates leukocytes. It activates osteoclasts. It activates stromal cells, epithelial cells in the gut, keratinocytes in the skin. But over the last number of years, particularly with the resolution of the Human Genome Project, we've come to recognize large families of cytokines, generally named for their structural homology. Let's think about the IL-17 superfamily. There are 6 members, of which I think we should probably focus on 2, IL-17A and IL-17F. There's one other I'll mention to you. It's quite interesting in the area of axSpA, IL-17E, also known as IL-25. [1,2] As we start to understand the pathways that drive that, and understand that those pathways talk to the immune system constantly, that raises huge opportunities for the future.