Mapping the immunological homunculus

Abstract

During the first century, the Roman physician Cornelius Celsus defined four cardinal signs of inflammation: redness, swelling, heat, and pain. These signs and symptoms occur during infection by invasive pathogens or as a consequence of trauma. Today, we understand the molecular basis of these physiological responses as mediated by cytokines and other factors produced by cells of the innate immune system. Cytokines are both necessary and sufficient to cause pathophysiological alterations manifested as the four cardinal signs. Importantly, this knowledge has enabled the development of highly selective therapeutical agents that target individual cytokines to prevent or reverse inflammation. For example, selective inhibitors of TNF, a major inflammatory cytokine, have revolutionized the therapy of rheumatoid arthritis, inflammatory bowel disease, and other autoimmune and autoinflammatory diseases affecting millions worldwide. Now, in PNAS, Hess et al. (1) use functional MRI to monitor brain activity and report that patients with rheumatoid arthritis who receive anti-TNF develop significant changes in brain activity before resolution of inflammation in the affected joints.