PT  - JOURNAL ARTICLE
AU  - Theoharis C Theoharides
AU  - Anastasia I Petra
AU  - Alexandra Taracanova
AU  - Smaro Panagiotidou
AU  - Pio Conti
TI  - The importance of IL-33 in allergic inflammation
AID  - 10.1124/jpet.114.222505
DP  - 2015 Jan 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - jpet.114.222505
4099  - http://jpet.aspetjournals.org/content/early/2015/04/23/jpet.114.222505.short
4100  - http://jpet.aspetjournals.org/content/early/2015/04/23/jpet.114.222505.full
AB  - IL-33 belongs to the IL-1 family of cytokines. While 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 "alarmin" signal 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 (SP) 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 Sjogren'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, they are 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.