Volume 12 Issue 1, January 2016

Glucocorticoids are the mainstay of treatment for patients with polymyalgia rheumatica (PMR) and often produce substantial clinical improvements, but treatment can be complicated by relapse, adverse effects of therapies, and concomitant conditions. New recommendations aim to guide clinicians and improve the management of this disorder.

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.

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.

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.

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.

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.

The contributions of key cytokines in rheumatoid arthritis (RA) pathogenesis, including TNF, IL-1, JAK-dependent cytokines, GM-CSF and chemokines, can be considered not only individually, but also in the context of an overall 'RA tissue response'. In this Opinion article, the authors provide an overview of the roles of cytokines in the innate, adaptive and stromal immune responses, and discuss how systematic analysis of cytokine pathways could yield new insights into disease pathogenesis and facilitate stratification for therapy.