PT - JOURNAL ARTICLE AU - Theoharis C. Theoharides AU - Anastasia I. Petra AU - Alexandra Taracanova AU - Smaro Panagiotidou AU - Pio Conti TI - Targeting IL-33 in Autoimmunity and Inflammation AID - 10.1124/jpet.114.222505 DP - 2015 Jul 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 24--31 VI - 354 IP - 1 4099 - http://jpet.aspetjournals.org/content/354/1/24.short 4100 - http://jpet.aspetjournals.org/content/354/1/24.full SO - J Pharmacol Exp Ther2015 Jul 01; 354 AB - Interleukin-33 (IL-33) belongs to the IL-1 family of cytokines. Whereas IL-1 is processed and released by live immune cells in response to infection or other triggers, IL-33 is mostly released as a danger signal (“alarmin”) from damaged cells. IL-33 may also be processed and released from activated mast cells (MCs) with subsequent autocrine and paracrine actions. IL-33 augments the stimulatory effects of IgE and substance P on MCs but can also trigger release of cytokines from MCs on its own. Blood IL-33 levels are increased in asthma, atopic dermatitis, multiple sclerosis, rheumatoid arthritis, and Sjögren's syndrome. However, prolonged elevation of IL-33 downregulates FcεRI and may be protective in atherosclerosis, suggesting different roles in immune-regulated diseases. Even though neutralizing IL-33, knocking-down its receptor, or using its soluble “decoy” receptor has resulted in anti-inflammatory effects, there appear to be different outcomes in different tissues. Hence, selective regulation of IL-33 synthesis, release, and signaling may be required to provide effective treatment options.