The IL-1 family and inflammatory diseases.

Abstract

IL-1 and its related family member IL-18 are primarily proinflammatory cytokines by their ability to stimulate the expression of genes associated with inflammation and autoimmune diseases. For IL-1 (IL-1alpha and IL-1beta), the most salient and relevant properties are the initiation of cyclooxygenase type 2 (COX-2), type 2 phospholipase A and inducible nitric oxide synthase (iNOS). This accounts for the large amount of prostaglandin-E2 (PGE2), platelet activating factor and nitric oxide (NO) produced by cells exposed to IL-1 or in animals or humans injected with IL-1. Another important member of the proinflammatory IL-1 family is IL-18. IL-18 is also an important player in autoimmune disease because of its ability to induce IFNgamma, particularly in combination with IL-12 or IL-15. Both IL-1 and IL-18 increase the expression of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) on mesenchymal cells and vascular-cell adhesion molecule-1 (VCAM-1) on endothelial cells. This latter property promotes the infiltration of inflammatory and immunocompetent cells into the extravascular space. IL-1 and IL-18 are also an angiogenic factors by increasing the expression of vascular endothelial growth factor; IL-1 and IL-18 thus play a role in pannus formation and blood vessel supply. The strongest case for the importance of IL-1 in disease processes come from the administration of the IL-1 receptor antagonist, also a member of the IL-1 family and IL-18 binding protein (IL-18BP), a constitutively expressed and secreted protein that binds and neutralizes IL-18. Data from the human genome project have revealed other members of the IL-1 family. However, these appear to be antagonists rather than agonists. IL-1 also acts as an adjuvant during antibody production and stimulates bone marrow stem cells for differentiation in the myeloid series. IL-1 is distinct from tumor necrosis factor (TNF); IL-1 and TNFalpha share several biological properties but the salient difference is that TNF receptor signaling induces programmed cell death whereas IL-1 receptor signaling does not. In fact, IL-1 is a hematopoietic growth factor and IL-1 was administered to humans to reduce the nadir of white blood cells and platelets in patients during bone-marrow transplantation. This property, of IL-1 is not observed in the responses to TNFalpha. Furthermore, in animal models of destructive rheumatoid arthritis, IL-1 is necessary but TNFalpha is not.

• Authors: C A Dinarello
• Journal: Clinical and experimental rheumatology (Clin Exp Rheumatol) 2002 Sep-Oct Vol. 20 Issue 5 Suppl 27 Pg. S1-13 ISSN: 0392-856X [Print] Italy
• PMID: 14989423 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S., Review)

Chemical References

• Interleukin-1
• Interleukin-18
• Isoenzymes
• Ligands
• Membrane Proteins
• Platelet Activating Factor
• Receptors, Interleukin-1
• Nitric Oxide
• NOS2 protein, human
• Nitric Oxide Synthase
• Nitric Oxide Synthase Type II
• Nos2 protein, mouse
• Cyclooxygenase 2
• PTGS2 protein, human
• Prostaglandin-Endoperoxide Synthases
• Phospholipases A
• Dinoprostone

Topics

• Animals
• Autoimmune Diseases (immunology)
• Cyclooxygenase 2
• Dinoprostone (immunology)
• Humans
• Interleukin-1 (immunology)
• Interleukin-18 (immunology)
• Isoenzymes (immunology)
• Ligands
• Membrane Proteins
• Mice
• Nitric Oxide (immunology)
• Nitric Oxide Synthase (immunology)
• Nitric Oxide Synthase Type II
• Phospholipases A (immunology)
• Platelet Activating Factor (immunology)
• Prostaglandin-Endoperoxide Synthases (immunology)
• Receptors, Interleukin-1 (immunology)