Pound the alarm: danger signals in rheumatic diseases

Damage-associated molecular patterns (DAMPs) are chemically heterogeneous endogenous host molecules rapidly released from damaged or dying cells that incite a sterile inflammatory response mediated via pattern recognition receptors (PRRs). The sources of DAMPs are dead or dying cells or the extracellular matrix and can signal through the PRRs, the Toll-like receptors or cytosolic Nod-like receptors, culminating in nuclear factor κB (NF-κB) activation and pro-inflammatory cytokine secretion. Together, these molecules are involved in sterile inflammation and many are associated with rheumatic autoimmune diseases such as rheumatoid arthritis, systemic lupus erythromatosus, psoriatic arthritis and systemic sclerosis. These diseases are associated with inflammation and many danger signals are found in sites of sterile inflammation and mediate inflammation. The present review examines the role of DAMPs in rheumatic conditions and suggests avenues for their therapeutic modulation.