Reviewer: S. Randhawa, M.D., Fellow, LSU (Shreveport) Department of Allergy & Immunology
Interleukin-1 (IL-1) is one of the first cytokines ever described. Since IL-1 can induce fever, affect lymphocytes, increase the number of bone marrow cells and cause degeneration of bone joints, several names were coined including endogenous pyrogen, lymphocyte activating factor, haemopoetin-1 and mononuclear cell factor.
IL-1 exists in two forms: IL-1α and IL-1β.
Source: monocytes, PMNs, epithelial cells;
Receptor: IL-1 binds to type I IL-1 receptor, this leads to MyD88 recruitment, activation of protein kinases (IRAK4, IRAK1 and TRAF6), and then activation of NFκB.
TLR3 signaling is mediated by toll-interleukin-1-receptor domain containing adapter inducing interferon β (TRIF) and is MyD88-independent.
Cytokine receptors (click to enlarge the image).
Effects: IL-1 mediates local inflammation, induces fever and synthesis of acute phase reactants by the liver (via IL-6 production)
IL-1 is composed of 2 distinct proteins called IL-1α and IL-1β.
Interleukin-1 superfamily
IL-1 Receptor antagonist (IL-1RA) competes for receptor binding with IL-1α and IL-1β, blocking their role in immune activation.
Interleukin-1 superfamily includes:
- IL-1α
- IL-1β and IL-1RA
- IL1F5, IL1F6, IL1F7, IL1F8, IL1F9, and IL1F10
- IL-33
- IL-18
IL-1α, IL-1β, and IL-1RA have been renamed IL-1F1, IL-1F2, and IL-1F3.
IL-33 is also called IL-1F11.
IL-1 family nomenclature
Newly cloned interleukin 1 (IL-1) family members1, 2, 3 were originally given an IL-1 family (IL-1F) designation, but as functions have now been elucidated for several of these, some researchers have proposed that each now be assigned an individual interleukin designation. IL-1F6, IL-1F8 and IL-1F9 are encoded by distinct genes but use the same receptor complex (IL-1Rrp2 and AcP), are proinflammatory and deliver nearly identical signals (http://goo.gl/X7ai).
IL-18
IL-18 is a proinflammatory cytokine. IL-18 works together with IL-12 to induce cell-mediated immunity following infection with microbial products like lipopolysaccharide (LPS)
IL-18 and IL-12 inhibit IL-4 dependent IgE and IgG1 production, and enhance IgG2a production in B cells.
IL-18 binding protein (IL18BP) binds and blocks IL-18.
Whereas IL-1 and IL-18 promote proinflammatory and TH1-associated responses, IL-33 induces the production of TH2-associated cytokines.
Medications
Treatment of CAPS
Anakinra (IL-1RA) is an IL-1 receptor antagonist that inhibits IL-1. Recombinant IL-1Ra or Anakinra (Kineret) is available commercially to treat systemic juvenile rheumatoid arthritis (JRA). Live vaccines should not be given concurrently with Anakinra.
Canakinumab is a human anti–interleukin-1β monoclonal antibody. Treatment with subcutaneous canakinumab once every 8 weeks was associated with a rapid remission of symptoms in most patients with CAPS.
Rilonacept (Arcalyst), is a dimeric fusion protein. IL-1 Trap or Rilonacept (Arcalyst) is used for management of cryopyrin-associated periodic syndromes (CAPS). Patients must me evaluated for latent TB before initiating therapy. Live vaccines should not be given concurrently. Taking rilonacept with TNF inhibitors is not recommended and may increase the risk of serious infections.
Anakinra (IL-1RA) is an IL-1 receptor antagonist that inhibits IL-1. Recombinant IL-1Ra or Anakinra (Kineret) is available commercially to treat systemic juvenile rheumatoid arthritis (JRA). Live vaccines should not be given concurrently with Anakinra.
Canakinumab is a human anti–interleukin-1β monoclonal antibody. Treatment with subcutaneous canakinumab once every 8 weeks was associated with a rapid remission of symptoms in most patients with CAPS.
Rilonacept (Arcalyst), is a dimeric fusion protein. IL-1 Trap or Rilonacept (Arcalyst) is used for management of cryopyrin-associated periodic syndromes (CAPS). Patients must me evaluated for latent TB before initiating therapy. Live vaccines should not be given concurrently. Taking rilonacept with TNF inhibitors is not recommended and may increase the risk of serious infections.
The cytokine interleukin-33 mediates anaphylactic shock. Pushparaj PN, Tay HK, H'ng SC, Pitman N, Xu D, McKenzie A, Liew FY, Melendez AJ. Proc Natl Acad Sci U S A. 2009 Jun 16;106(24):9773-8. Epub 2009 Jun 8.
Interleukin 33 (IL-33)
Published: 08/25/2009
Updated: 09/27/2010
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