alarmen

Alarmins, in immunology, refer to endogenously derived molecules that signal tissue and cellular damage to the immune system, thereby initiating and shaping inflammatory responses. They are also described as danger-associated molecular pattern molecules (DAMPs). Unlike pathogen-associated molecular patterns (PAMPs), alarmins originate from the host and can trigger inflammation even in the absence of infection. When released by stressed or dying cells, alarmins engage pattern recognition receptors such as Toll-like receptors (TLRs) and the receptor for advanced glycation end products (RAGE), activating signaling pathways like NF-κB and inflammasomes and promoting the production of cytokines and chemokines.

Common examples of alarmins include HMGB1 (high mobility group box 1), heat-shock proteins (such as HSP60 and HSP70), IL-1α, IL-33, and S100 family proteins (notably S100A8/A9, also known as calprotectin). Extracellular nucleic acids and ATP are also considered alarmins in certain contexts. Alarmins can be passively released by necrotic cells or actively secreted by immune and non-immune cells in response to stress, infection, or injury.

Physiological and clinical significance: alarmins help coordinate early immune responses to tissue injury and sterile inflammation, contributing to defense against pathogens and to tissue repair processes. However, excessive or misdirected alarmin signaling is implicated in inflammatory and autoimmune diseases, ischemia-reperfusion injury, and trauma. Consequently, alarmins are studied as biomarkers of tissue damage and as potential targets for therapeutic modulation to mitigate inflammatory pathology.

Note: In broader discussions of sterile inflammation, the term alarmins is often used alongside DAMPs; some molecules may be categorized differently depending on context.