Multiple inflammatory signaling pathways and cytokine networks

Multiple inflammatory signaling pathways and cytokine networks refers to the complex, interconnected web of intracellular cascades and extracellular proteins that regulate the body's immune and inflammatory responses. This system includes major signaling axes such as the NF-κB, JAK-STAT, MAPK, and NLRP3 inflammasome pathways, which are activated by pattern recognition receptors (PRRs) or cytokine receptors [1][2]. These pathways drive the expression and secretion of various cytokines, including TNF-α, IL-1, IL-6, and IL-17, which further amplify the inflammatory signal through autocrine and paracrine loops [3]. Dysregulation of these networks is a primary driver of chronic inflammatory diseases like rheumatoid arthritis and Crohn's disease, as well as acute conditions like cytokine release syndrome (CRS) [4]. While the term itself is too broad to represent a single drug target, it encompasses numerous validated targets for which biologicals and small molecules have been developed, such as TNF inhibitors and JAK inhibitors [5]. Therapeutic strategies often aim to selectively inhibit specific nodes within these networks to suppress pathological inflammation while maintaining sufficient immune surveillance. Consequently, this entry describes a physiological system rather than a discrete molecular target suitable for specific pharmacological profiling. Citations: [1] Liu, T., et al. (2017). NF-κB signaling in inflammation. Signal Transduction and Targeted Therapy. [2] Hu, X., et al. (2021). The JAK-STAT pathway in health and disease. Nature Reviews Rheumatology. [3] Dinarello, C. A. (2011). Interleukin-1 in the pathogenesis and treatment of inflammatory diseases. Blood. [4] Feldmann, M., & Maini, R. N. (2003). TNF defined as a therapeutic target for rheumatoid arthritis and beyond. Nature Medicine. [5] O'Shea, J. J., et al. (2013). The JAK-STAT pathway: biology, therapeutics and beyond. Nature Reviews Drug Discovery.

Other names

Inflammatory cascadeCytokine signaling networkPro-inflammatory signaling pathwaysInflammatory milieu

Modulation of immune signaling through cytokine neutralization, receptor antagonism, or intracellular kinase inhibition.