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INTERLEUKINS AND INTERFERONS
|White blood cells (leukocytes) are involved in a variety of reactions against pathogens and abnormal body cells. There are a number of proteins which signal these white blood cells, and many of these signals have been conserved in higher vertebrates. Below are images of blood (including white blood cells) isolated from a fish, frog, and turtle.|
In mammals, local hormones known as cytokines regulate both innate and adaptive immune reactions. Those cytokines which act on leukocytes are called interleukins. Many interleukins are members of the 4 α-helical bundle cytokine family (Kaiser, 2004). There are only a few thousand protein domains known in living organisms. Only 7% are unique to vertebrates. In humans, many of the new domains function in the immune system, such as the cytokine domain (with in at least 42 genes) and the interleukin-1 domain (in at least 7 genes) (Liu, 2001). The interleukin-1 genes form a family. The members of the IL-10 family are located in 2 clusters. IL10, IL19, IL20, and IL24 exist on chromosome 1 and IL22, and IL26 are found on chromosome 12. IL10 family members are only known in amniotes (Kaiser, 2004). A number of interleukin genes with a conserved intron-exon structure exist a cluster on chromosome 2q (Smith, 2000). There is evidence for the existence of IL-1 like proteins in protostomes and primitive deuterostomes (Magor, 2001). Much of the expansion of the expansion of the interleukin family has occurred recently in separate events in early vertebrates and mammals (Huising, 2004).
INTERLEUKIN 1-ALPHA; IL1A
IL1A activates transcription factors which cause inflammation and is produced by macrophages, keratinocytes, fibroblasts, and B lymphocytes. Certain alleles have been linked to rheumatoid arthritis, peridontitis, and Alzheimers. Insects seem to possess molecules similar to IL-1α (Kaiser, 2004).
INTERLEUKIN 1-BETA; IL1B
IL1B plays a role in the adhesion of tumor cells in capillary endothelia and melanomas. Microglia can release this interleukin and it may be involved in multiple sclerosis. It has a role in bone reabsorption and may be involved in osteoporosis. Mutations can increase the risk of gastric cancer after infection. IL-1β is known in gnathostomes (Kaiser, 2004).
INTERLEUKIN 2; IL2
IL2 was formerly called T cell growth factor. IL2 and 15 use the same β and γ chains but differ in their α chains. They are only known in amniotes. IL2 stimulates T cell production (Kaiser, 2004).
INTERLEUKIN 3; IL3
IL3 is a factor controlling hematopoeisis of lymphoid cells and mast cells. It is also expressed in astrocytes where it functions in neurodegeneration and repair.
INTERLEUKIN 4; IL4
is involved in bone loss and offers protection from
INTERLEUKIN 5; IL5
IL5 is also known as the eosinophil differentiation factor. Overproduction of this interleukin increases the production of eosinophils. It is the main regulatory factor of eosinophil development and IgA production. IL5 functions in the activation and responses of eosinphils and basophils. In chickens, IL5 may be a pseudogene and chickens may lack eosinophils (Kaiser, 2004). The following image is of a human eosinophil.
INTERLEUKIN 6; IL6
IL6 polymorphisms affect susceptibility to Kaposi sarcoma and osteoporosis. Higher levels may play a role in some cancers. Mutant mice suffer liver failure. Interleukin-6 is only known from mammals (Magor, 2001).
INTERLEUKIN 7; IL7
IL7 regulates interstitial mucosal lymphocytes and hematopoeisis.
INTERLEUKIN 8; IL8
IL8 activates neutrophils. IL-8 vertebrates (Kaiser, 2004).
INTERLEUKIN 9; IL9
IL9 is involved in allergic reactions of the bronchi.
INTERLEUKIN 10; IL10
IL10 blocks atheroscleosis and is anti-inflammatory.
INTERLEUKIN 11; IL11
IL11 is involved in B cell development.
INTERLEUKIN 12A; IL12A
IL12A stimulates T cells and natural killer cells. IL12 is produced by antigen presenting cells after infection and activates NK cells and T cells. It is composed of two chains encoded by two genes. IL-12 is only known in amniotes (Kaiser, 2004).
INTERLEUKIN 12B; IL12B
IL12B is made by macrophages and functions in cell mediated immunity.
INTERLEUKIN 13; IL13
IL13 regulates inflammatory reactions. Polymorphisms affect the susceptibility to asthma and allergic rhinitis.
INTERLEUKIN 14; IL14
IL14 is produced by T cells.
INTERLEUKIN 15; IL15
IL15 functions in T cell activation.
INTERLEUKIN 16; IL16
IL16 attracts lymphatic cells.
INTERLEUKIN 17; IL17
IL17 increases the synthesis of prostaglandin E2 and plays a role in autoimmune arthritis.
INTERLEUKIN 17B; IL17B
IL17B functions in the pancreas, small intestine, and stomach. The following image is of leukocytes in a Peyers patch of the small intestine.
INTERLEUKIN 17C; IL17C
IL17c is not yet known in adult tissues.
INTERLEUKIN 17D; IL17D
IL17D is found in a variety of tissues.
INTERLEUKIN 17F; IL17F
IL17F is produced by mast cells and functions in a number of tissues where it inhibits endothelial angiogenesis.
INTERLEUKIN 17E; IL17E
IL17E is expressed in the colon, uterus, kidney, lung, stomach, and small intestine.
INTERLEUKIN 18; IL18
IL18 stimulates natural killer cells. It is involved in inflammatory skin reactions and graft vs. host disease. IL18 is only known in amniotes (Kaiser, 2004).
INTERLEUKIN 19; IL19
IL19 is produced by monocytes, such as that depicted in the following image.
INTERLEUKIN ; IL20
IL20 is expressed in the skin and the trachea.
INTERLEUKIN 21; IL21
IL21 functions in B cell proliferation.
INTERLEUKIN 22; IL22
functions in anti-inflammatory responses.
Interleukin-22 and -26 are now known in teleost fish; they were previously described only in mammals (Igawa, 2006).
INTERLEUKIN 23; IL23
Il23 increases the secretion of interferon.
INTERLEUKIN 24; IL24
IL24 controls cell growth and differentiation and can induce apoptosis.
INTERLEUKIN 26; IL26
INTERLEUKIN 28A; IL28A
IL28A is a class II interleukin which is related to the interferons.
INTERLEUKIN 28B; IL28B
IL28B is a class II interleukin which is related to the interferons.
INTERLEUKIN 29; IL29
IL29 is a class II interleukin which is related to the interferons.
INTERLEUKIN 30; IL30
IL30 affects T cells.
INTERLEUKIN 1 FAMILY, MEMBER 5; IL1F5
INTERLEUKIN 1 FAMILY, MEMBER 6; IL1F6
IL1F6 is expressed in the immune system and the fetal brain. The developing brain of a chick is depicted below.
INTERLEUKIN 1 FAMILY, MEMBER 7; IL1F7
IL1F7 is expressed in keratinocytes.
INTERLEUKIN 1 FAMILY, MEMBER 8; IL1F8
IL1F8 is expressed in the tonsils, bone marrow, placenta, lung, and colon.
INTERLEUKIN 1 FAMILY, MEMBER 9; IL1F9
IL1F9 is expressed in the squamous epithelia of the esophagus.
The diverse genes of the interferon gene family in mammals have arisen through gene duplication and gene conversion (Woelk, 2007). There are 26 intereferon genes in a cluster on chromosome 9. These genes lack intervening sequences. The order of the genes in the cluster is 9p.pter-B1---W1---A21---WP15---A4---W9---A7---A10---WP18---AP16---A17---A14---A22---A5---AP20---A6---A13---A2---A8---W2---WP19---A1---centromere. Interferons bind with the IFN-αβ receptor (OMIM; Sheppard, 2003). ILN-28 and 29 are more similar to interleukin 10 in their gene sequence but more like interferons in their amino acid sequences and in some of their functions. They represent links between interferons and the interleukin 10 family (Sheppard, 2003). Interferons are definitely known from amniotes and possible homologs have also been identified in fish (Magor, 2001). The IFNα family seems to have arisen from after the primate lineage arose (Gillespie, 1983).
INTERFERON, ALPHA-1; IFNA1
Mutations in humans which prevent secretion of IFNA1 result in persistent infections and the lack of natural killer cell activity.
INTERFERON, ALPHA-2; IFNA2
IFNA2 is used in the treatment of hemangioma, hepatic metastasis, and melanoma.
INTERFERON, ALPHA-4; IFNA4
INTERFERON, ALPHA-5; IFNA5
INTERFERON, ALPHA-6; IFNA6
INTERFERON, ALPHA-7; IFNA7
INTERFERON, ALPHA-8; IFNA8
INTERFERON, ALPHA-10; IFNA10
INTERFERON, ALPHA-13; IFNA13
INTERFERON, ALPHA-14; IFNA14
INTERFERON, ALPHA-16; IFNA16
INTERFERON, ALPHA-17; IFNA17
INTERFERON, ALPHA-P20; IFNAP20
INFAP20 is a pseudogene.
INTERFERON, ALPHA-21; IFNA21
INTERFERON, ALPHA-P22; IFNAAP22
INFAP22 is a pseudogene.
INTERFERON, BETA-1; IFNB1
IFNB1 inhibits the differentiation of osteoclasts. With INFA1 it is involve in promoting p53 transcription for apoptosis in virally infected cells.
INTERFERON, GAMMA-1; IFNG1
INFNG1 is not detected in HIV patients and in those who are immunocompromised. Without this interferon, patients suffer from persistent infections. Mutations in this gene increase susceptibility to tuberculosis and angiomyolipoma.
INTERFERON, OMEGA-1; IFNW1
IFNW1 may be the only functional omega gene.
INTERFERON, OMEGA-2; IFNW2
INTERFERON, OMEGA-P2; IFNWP2
IFNWP2 is a pseudogene.
INTERFERON, OMEGA-P15; IFNWP15
IFNWP15 is a pseudogene.
INTERFERON, OMEGA-P18; IFNWP18
IFNWP18 is a pseudogene.
INTERFERON, OMEGA-P19; IFNWP19
IFNWP19 is a pseudogene.