Focus |

Cytokines in disease

Cytokines are key mediators of inflammation prominently involved in autoimmune and inflammatory diseases. The cytokines of most relevance to rheumatic diseases also have important functions in many non-immune cell types, including fibroblasts, osteoblasts, osteoclasts and endothelial cells, beyond their well-described roles in the immune system. Advances in our understanding of cytokine biology are not only improving our knowledge of the pathogenetic mechanisms of diseases such as rheumatoid arthritis, osteoarthritis and systemic lupus erythematosus—disorders in which cytokines play a key part—but also driving the development of new therapeutic strategies. This fast-developing area of research is achieving notable success with approaches targeting cytokine-mediated mechanisms, and multiple studies are now underway to test the efficacy of cytokine signalling modulation in disease. In this Focus issue, the cytokine pathways at work in rheumatic diseases are explored, with an emphasis on the role of TNF, IL-1, GM-CSF, chemokines and type I and II cytokines in supporting inflammation and tissue destruction.

Content

  • Nature Reviews Rheumatology | Review Article

    Chemokines and their receptors are involved in the pathogenesis of rheumatoid arthritis. Therapeutic strategies targeting chemokine pathways have had promising results in animal models, but have been less successful in human trials. Szekanecz and Koch discuss the different approaches to chemokine-pathway targeting and the possible reasons for the difficulty in developing effective therapies.

    • Zoltán Szekanecz
    •  &  Alisa E. Koch
  • Nature Reviews Rheumatology | Review Article

    Members of the IL-1 family of cytokines have been implicated in several autoimmune diseases, including rare hereditary syndromes and more frequent diseases such as gout. Once processed and activated, IL-1α and IL-1β promote inflammation, monocyte and neutrophil infiltration and, ultimately, tissue damage and stress. Therapies that target IL-1 have already shown clinical efficacy, and are enabling a better understanding of the biology of this cytokine family.

    • Georg Schett
    • , Jean-Michel Dayer
    •  &  Bernhard Manger
  • Nature Reviews Rheumatology | Review Article

    Cytokines that signal via the Janus kinase (JAK) and signal transducer and activator of transcription (STAT) pathway have diverse roles in normal immune responses as well as immune-mediated diseases. This Review provides an overview of these roles as well as the JAK–STAT pathway, and discusses emerging therapies that block JAKs and the cytokines that signal through them.

    • Daniella M. Schwartz
    • , Michael Bonelli
    • , Massimo Gadina
    •  &  John J. O'Shea
  • Nature Reviews Rheumatology | Review Article

    Granulocyte-macrophage colony stimulating factor (GM-CSF) is a cytokine with a wide range of biological effects that span innate and adaptive immunity processes. As our knowledge of the biology of GM-CSF improves, its potential as a therapeutic target in rheumatic diseases is being acknowledged, and the first early phase clinical trials of GM-CSF inhibition in patients with inflammatory disorders have produced encouraging results.

    • Ian P. Wicks
    •  &  Andrew W. Roberts
  • Nature Reviews Rheumatology | Review Article

    Despite the clinical success of therapeutics that inhibit TNF, gaps remain about the biology of this pleiotropic cytokine. This Review explores the latest discoveries related to TNF signalling pathways, TNF-induced gene expression, and the homeostatic and pathogenic functions of TNF, as well as the implications of these findings for therapeutics for TNF-mediated diseases.

    • George D. Kalliolias
    •  &  Lionel B. Ivashkiv