Interleukin 18
Encyclopedia
Interleukin-18 also known as IL18 is a protein
which in humans is encoded by the IL18 gene
. The protein encoded by this gene is a proinflammatory cytokine
.
that belongs to the IL-1
superfamily and is produced by macrophage
s and other cells. IL-18 works by binding to the interleukin-18 receptor
, and together with IL-12
it induces cell-mediated immunity
following infection with microbial products like lipopolysaccharide
(LPS). After stimulation with IL-18, natural killer (NK) cells and certain T cells release another important cytokine called interferon-γ
(IFN-γ) or type II interferon that plays an important role in activating the macrophages or other cells.
The combination of this cytokine and IL12 has been shown to inhibit IL4
dependent IgE
and IgG1
production, and enhance IgG2a production in B cell
s. IL-18 binding protein (IL18BP
) can specifically interact with this cytokine, and thus negatively regulate its biological activity.
, which suggests its role in certain inflammatory disorders.
Endometrial IL-18 receptor mRNA and the ratio of IL-18 binding protein
to interleukin 18 are significantly increased in adenomyosis
patients in comparison to normal people, indicating a role in its pathogenesis.
IL-18 has been implicated as an inflammatory mediator of Hashimoto's thyroiditis
, the most common cause of autoimmune hypothyroidism. IL-18 is up regulated by interferon-gamma
.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
which in humans is encoded by the IL18 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
. The protein encoded by this gene is a proinflammatory cytokine
Proinflammatory cytokine
A proinflammatory cytokine is a cytokine which promotes systemic inflammation.Examples include IL-1 and TNF alpha....
.
Function
IL-18 is a cytokineCytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
that belongs to the IL-1
IL-1
IL-1 may refer to:* Interleukin 1, a protein* Illinois' 1st congressional district* Illinois Route 1* Building 1 of Infinite Loop , the Headquarters of Apple Inc....
superfamily and is produced by macrophage
Macrophage
Macrophages are cells produced by the differentiation of monocytes in tissues. Human macrophages are about in diameter. Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense as well as help initiate specific defense mechanisms of vertebrate animals...
s and other cells. IL-18 works by binding to the interleukin-18 receptor
Interleukin-18 receptor
The interleukin-18 receptor is an interleukin receptor of the immunoglobulin superfamily. IL-18R is a heteromeric complex of alpha- and beta-chains encoded by the genes and respectively....
, and together with IL-12
Interleukin 12
Interleukin 12 is an interleukin that is naturally produced by dendritic cells, macrophages and human B-lymphoblastoid cells in response to antigenic stimulation.-Gene and structure:...
it induces cell-mediated immunity
Cell-mediated immunity
Cell-mediated immunity is an immune response that does not involve antibodies but rather involves the activation of macrophages, natural killer cells , antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines in response to an antigen...
following infection with microbial products like lipopolysaccharide
Lipopolysaccharide
Lipopolysaccharides , also known as lipoglycans, are large molecules consisting of a lipid and a polysaccharide joined by a covalent bond; they are found in the outer membrane of Gram-negative bacteria, act as endotoxins and elicit strong immune responses in animals.-Functions:LPS is the major...
(LPS). After stimulation with IL-18, natural killer (NK) cells and certain T cells release another important cytokine called interferon-γ
Interferon-gamma
Interferon-gamma is a dimerized soluble cytokine that is the only member of the type II class of interferons. This interferon was originally called macrophage-activating factor, a term now used to describe a larger family of proteins to which IFN-γ belongs...
(IFN-γ) or type II interferon that plays an important role in activating the macrophages or other cells.
The combination of this cytokine and IL12 has been shown to inhibit IL4
Interleukin 4
Interleukin-4, abbreviated IL-4, is a cytokine that induces differentiation of naive helper T cells to Th2 cells. Upon activation by IL-4, Th2 cells subsequently produce additional IL-4. The cell that initially produces IL-4, thus inducing Th0 differentiation, has not been identified, but recent...
dependent IgE
Immunoglobulin E
Immunoglobulin E is a class of antibody that has been found only in mammals. IgE is a monomeric antibody with 4 Ig-like domains...
and IgG1
Immunoglobulin G
Immunoglobulin G are antibody molecules. Each IgG is composed of four peptide chains — two heavy chains γ and two light chains. Each IgG has two antigen binding sites. Other immunoglobulins may be described in terms of polymers with the IgG structure considered the monomer.IgG constitutes 75%...
production, and enhance IgG2a production in B cell
B cell
B cells are lymphocytes that play a large role in the humoral immune response . The principal functions of B cells are to make antibodies against antigens, perform the role of antigen-presenting cells and eventually develop into memory B cells after activation by antigen interaction...
s. IL-18 binding protein (IL18BP
IL18BP
Interleukin-18-binding protein is a protein that in humans is encoded by the IL18BP gene.-Further reading:...
) can specifically interact with this cytokine, and thus negatively regulate its biological activity.
Clinical significance
Apart from its physiological role, IL-18 is also able to induce severe inflammatory reactionsInflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
, which suggests its role in certain inflammatory disorders.
Endometrial IL-18 receptor mRNA and the ratio of IL-18 binding protein
IL18BP
Interleukin-18-binding protein is a protein that in humans is encoded by the IL18BP gene.-Further reading:...
to interleukin 18 are significantly increased in adenomyosis
Adenomyosis
Adenomyosis is a medical condition characterized by the presence of ectopic glandular tissue found in muscle. The term adenomyosis is derived from the terms adeno- , myo- , and -osis...
patients in comparison to normal people, indicating a role in its pathogenesis.
IL-18 has been implicated as an inflammatory mediator of Hashimoto's thyroiditis
Hashimoto's thyroiditis
Hashimoto's thyroiditis or chronic lymphocytic thyroiditis is an autoimmune disease in which the thyroid gland is gradually destroyed by a variety of cell- and antibody-mediated immune processes. It was the first disease to be recognized as an autoimmune disease...
, the most common cause of autoimmune hypothyroidism. IL-18 is up regulated by interferon-gamma
Interferon-gamma
Interferon-gamma is a dimerized soluble cytokine that is the only member of the type II class of interferons. This interferon was originally called macrophage-activating factor, a term now used to describe a larger family of proteins to which IFN-γ belongs...
.