Inflammation signaling pathways

Inflammation signaling pathways are complex networks of molecular interactions that coordinate the body's response to harmful stimuli, such as pathogens, tissue injury, or irritants [11, 13]. These pathways, including the NF-κB, JAK-STAT, and MAPK cascades, are activated by cell-surface receptors like Toll-like receptors (TLRs) and cytokine receptors in response to inflammatory mediators [6, 14]. Once triggered, they lead to the production of pro-inflammatory cytokines, chemokines, and adhesion molecules that recruit and activate immune cells [5, 11]. While acute activation is essential for host defense and tissue repair, chronic or dysregulated signaling is a hallmark of numerous diseases, including rheumatoid arthritis, inflammatory bowel disease, and atherosclerosis [1, 13]. The resolution of inflammation is also an active process involving specific signaling pathways that restore tissue homeostasis [13]. Consequently, these pathways are major focal points for therapeutic intervention, with drugs designed to inhibit specific components like cytokines (e.g., TNF-α) or intracellular kinases (e.g., JAKs) to dampen the inflammatory response [1, 6]. However, broad inhibition of these pathways can lead to significant safety concerns, most notably an increased susceptibility to infections due to suppressed immune surveillance [1, 8].

Other names

Inflammatory signalingPro-inflammatory pathwaysInflammatory cascade

Drugs targeting these pathways typically act by inhibiting specific signaling nodes, such as cytokine receptors (e.g., TNFR, IL-6R), intracellular kinases (e.g., JAK, BTK, MAPK), or transcription factors (e.g., NF-κB), thereby reducing the production and action of pro-inflammatory mediators [1, 6, 7, 11].