Abstract
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.
Footnotes
- Received December 31, 2014.
- Accepted April 22, 2015.
T.C.T. is the recipient of U.S. Patent No. US2,013,011,5202 A1 and U.S. Patent Application No. US8,268,365 B2 covering the use of flavonoids in neuroinflammatory conditions. The remaining authors declare no conflicts of interest.
- Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics
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