The balance between IL-1 and IL-1Ra in disease.
IL-1 is an important mediator of inflammation and tissue damage in multiple organs, both in experimental animal models of disease and in human diseases. The IL-1 family consists of two agonists, IL-1alpha and IL-1beta, two receptors, biologically active IL-1RI and inert IL-1RII, and a specific receptor antagonist, IL-1Ra. The balance between IL-1 and IL-1Ra in local tissues plays an important role in the susceptibility to and severity of many diseases. An allelic polymorphism in the IL-1Ra gene has been associated with a variety of human diseases primarily of epithelial and endothelial cell origin. This association may be secondary to an imbalance in the IL-1 system with enhanced production of IL-1beta and reduced production of the major intracellular isoform of IL-1Ra. Treatment of RA with daily subcutaneous injections of recombinant IL-1Ra protein has been shown to be efficacious. Gene therapy approaches with IL-1Ra are being evaluated for the treatment of RA and other human diseases.
Arend
William P
WP
B115 Division of Rheumatology, Health Sciences Centre, University of Colorado, 4200 East Ninth Avenue, Denver, CO 80262, USA. william.arend@uchsc.edu
D000818:Animals; D001168:Arthritis / Q000628:therapy; D001327:Autoimmune Diseases / Q000503:physiopathology; D004195:Disease Models, Animal; D015316:Genetic Therapy; D006706:Homeostasis; D006801:Humans; D007239:Infections / Q000503:physiopathology; D007249:Inflammation / Q000503:physiopathology*; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009369:Neoplasms / Q000503:physiopathology; D011110:Polymorphism, Genetic; D020033:Protein Isoforms / Q000502:physiology; D011817:Rabbits; D017472:Receptors, Interleukin-1 / Q000502:physiology*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012098:Reproduction / Q000502:physiology; D012795:Sialoglycoproteins / Q000235:genetics / Q000502:physiology* / Q000627:therapeutic use
C507763:IL1RN protein, human; C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D020033:Protein Isoforms; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D012795:Sialoglycoproteins