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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.
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     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

IL4 is involved in bone loss and offers protection from Graves disease and autoimmune diseases.  A number of interleukins function in allergic responses and responses to extracellular parasites.  The switching of antibody classes from IgG to IgE requires IL4 and IL13 (Kaiser, 2004).

 

 

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.

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.

PEYER

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.

MONOCYTE

INTERLEUKIN ; IL20

IL20 is expressed in the skin and the trachea.

 

INTERLEUKIN 21; IL21

IL21 functions in B cell proliferation.

 

INTERLEUKIN 22; IL22

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.

EMBRYO

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.

 

INTERFERONS

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.