IL-1 pathways in inflammation and human diseases.
Interleukin (IL)-1 was first cloned in the 1980s, and rapidly emerged as a key player in the regulation of inflammatory processes. The term IL-1 refers to two cytokines, IL-1alpha and IL-1beta, which are encoded by two separate genes. The effects of IL-1 are tightly controlled by several naturally occurring inhibitors, such as IL-1 receptor antagonist (IL-1Ra), IL-1 receptor type II (IL-1RII), and other soluble receptors. Numerous IL-1 inhibitors have been developed and tested primarily in rheumatoid arthritis, with only modest effects. By contrast, the use of IL-1 antagonists has been uniformly associated with beneficial effects in patients with hereditary autoinflammatory conditions associated with excessive IL-1 signaling, such as cryopyrinopathies and IL-1Ra deficiency. Successful treatment with IL-1 blockers has also been reported in other hereditary autoinflammatory diseases, as well as in nonhereditary inflammatory diseases, such as Schnizler syndrome, systemic-onset juvenile idiopathic arthritis and adult Still disease. The role of microcrystals in the regulation of IL-1beta processing and release has provided the rationale for the use of IL-1 inhibitors in crystal-induced arthritis. Finally, preliminary results indicating that IL-1 targeting is efficacious in type 2 diabetes and smoldering myeloma have further broadened the spectrum of IL-1-driven diseases.
Gabay
Cem
C
Division of Rheumatology, University Hospitals of Geneva & Department of Pathology-Immunology, University of Geneva School of Medicine, 26 Avenue Beau-Séjour, 1211 Geneva 14, Switzerland. cem.gabay@hcuge.ch
Lamacchia
Céline
C
Palmer
Gaby
G
D000818:Animals; D015331:Cohort Studies; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000503:physiopathology; D018836:Inflammation Mediators / Q000097:blood; D053590:Interleukin 1 Receptor Antagonist Protein / Q000627:therapeutic use; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D053583:Interleukin-1beta / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D011379:Prognosis; D018123:Receptors, Interleukin / Q000037:antagonists & inhibitors / Q000187:drug effects; D012216:Rheumatic Diseases / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy*; D018570:Risk Assessment; D015398:Signal Transduction; D016896:Treatment Outcome
D018836:Inflammation Mediators; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D053583:Interleukin-1beta; D018123:Receptors, Interleukin