Therapeutic potential of targeting IL-1 and IL-18 in inflammation.
Interleukin (IL)-1 and IL-18 are cytokines that play a major role in autoimmune and inflammatory human disease. Both cytokines drive a wide range of pro-inflammatory effector networks in many cell types and use common signal transduction cascades. IL-1, IL-18 and other members of the IL-1 superfamily are expressed at elevated levels in tissue and fluid samples isolated from patients with many chronic inflammatory diseases. These cytokines are primary drivers in acute and chronic animal models of inflammation and their blockade has been shown to ameliorate disease in preclinical studies. Biological agents that target IL-1 have demonstrated efficacy in patients with rheumatoid arthritis, and further agents targeting IL-1 or IL-18 neutralisation are in clinical development. The potential for such agents spans human disease where tissue destruction is a primary end point of cytokine action.
Braddock
Martin
M
AstraZeneca R&D Charnwood, Disease Sciences Section, Discovery Bioscience Department, Bakewell Road, Loughborough, Leicestershire, LE11 5RH, UK. martin.braddock@astrazeneca.com
Quinn
Anthony
A
Canvin
Jan
J
D000906:Antibodies / Q000737:chemistry; D002986:Clinical Trials as Topic; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007249:Inflammation / Q000628:therapy*; D007375:Interleukin-1 / Q000378:metabolism*; D020382:Interleukin-18 / Q000378:metabolism*; D053727:Interleukin-18 Receptor alpha Subunit; D018123:Receptors, Interleukin / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000378:metabolism; D053724:Receptors, Interleukin-18; D015398:Signal Transduction; D013997:Time Factors
D000906:Antibodies; D016207:Cytokines; C508572:IL18R1 protein, human; D007375:Interleukin-1; D020382:Interleukin-18; D053727:Interleukin-18 Receptor alpha Subunit; D018123:Receptors, Interleukin; D017472:Receptors, Interleukin-1; D053724:Receptors, Interleukin-18