Tumor necrosis factor-alpha and interleukin-1 beta signaling pathways (TNF/IL-1 pathways)

The Tumor necrosis factor-alpha (TNF-alpha) and Interleukin-1 beta (IL-1beta) related pathways are critical signaling networks that mediate systemic inflammation and immune homeostasis. TNF-alpha and IL-1beta are primary pro-inflammatory cytokines produced mainly by activated macrophages and monocytes in response to pathogens or tissue damage [1][2]. These cytokines bind to their specific cell-surface receptors, such as TNFR1 and IL-1R1, to activate downstream transcription factors like NF-kappaB and AP-1, which drive the production of further inflammatory mediators [3]. Chronic overactivation of these pathways is implicated in the pathogenesis of various inflammatory conditions, including rheumatoid arthritis, psoriasis, and inflammatory bowel disease [4]. Pharmacological modulation of these pathways, primarily through the use of monoclonal antibodies or decoy receptors, has revolutionized the treatment of autoimmune disorders [5]. Despite their efficacy, targeting these pathways requires careful monitoring due to the increased risk of serious infections and potential for malignancy associated with prolonged immunosuppression [6]. [1] "Tumor Necrosis Factor (TNF)," StatPearls, https://www.ncbi.nlm.nih.gov/books/NBK482426/ [2] "Interleukin-1 Beta," PubChem, https://pubchem.ncbi.nlm.nih.gov/compound/Interleukin-1-beta [3] "Signaling by IL1 and TNF," Reactome, https://reactome.org/content/detail/R-HSA-446652 [4] "The role of TNF-alpha and IL-1beta in inflammation," PubMed, https://pubmed.ncbi.nlm.nih.gov/12794202/ [5] "Anti-TNF and Anti-IL-1 Therapies," American College of Rheumatology, https://www.rheumatology.org/I-Am-A/Patient-Care/Biologics [6] "Adverse effects of biologics," PubMed Central, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6322088/

Other names

TNF-alpha/IL-1beta axisPro-inflammatory cytokine pathwaysTNF-IL1 signalingTumor necrosis factor and interleukin-1 signaling

Inhibition of pro-inflammatory cytokine signaling by neutralizing ligands (Tumor necrosis factor-alpha or Interleukin-1 beta) or blocking their respective receptors (TNFR or IL-1R) to prevent downstream activation of NF-kappaB and MAPK pathways.