Izvorni kod stranice Interleukin 6

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'''Interleukin 6''' (IL-6) je [[protein]] koji je kod ljudi kodiran ''IL6'' [[gen]]om.<ref name="pmid3294161">{{cite journal | author = Ferguson-Smith AC, Chen YF, Newman MS, May LT, Sehgal PB, Ruddle FH | title = Regional localization of the interferon-beta 2/B-cell stimulatory factor 2/hepatocyte stimulating factor gene to human chromosome 7p15-p21 | journal = Genomics | volume = 2 | issue = 3 | pages = 203–8 | year = 1988 | month = April | pmid = 3294161 | doi = | url = | issn = }}</ref><ref>{{MireSluisCytokines}}</ref>

IL-6 je [[interleukin]] koji može da dejstvuje kao proinflamatorni i antiinflamatorni [[Citokini|citokin]]. On se izlučuje iz [[T ćelija]] i [[makrofag]]a. Ovaj citokin inicira imuni odgovor na traumu, posebno opekotine i druge oštete tkiva koje dovode do inflamacije.<ref name="KubyImmunology6th">{{KubyImmunology6th}}</ref> Za IL-6 je bilo pokazano kod miševa, da je on u pogledu odgovora domaćina na strane patogene neophodan za otpornost protiv bakterije ''[[Streptococcus pneumoniae]]''.<ref>{{cite journal | author=van der Poll T, Keogh CV, Guirao X, Buurman WA, Kopf M, Lowry SF | title=Interleukin-6 gene-deficient mice show impaired defense against pneumococcal pneumonia | url=https://archive.org/details/sim_journal-of-infectious-diseases_1997-08_176_2/page/439 | journal=J Infect Dis | year=1997| pages=439–44| volume=176| issue=2| pmid=9237710}}</ref> IL-6 je isto tako „miokin," citokin proizveden u mišićima, i njegova količina je povišena usled mišićnih kontrakcija.<ref>{{cite journal | author=Febbraio MA, Pedersen BK | title=Contraction-induced myokine production and release: is skeletal muscle an endocrine organ? | journal=Exerc Sport Sci Rev | year=2005 | pages=114–9 | volume=33 | issue=3 | pmid=16006818 | doi=10.1097/00003677-200507000-00003}}</ref> NJegova koncentracija je značajno povišena u toku treninga, i on prethodi pojavi drugih citokina u cirkulaciji. Za njega se misli da dejstvuje poput hormona koji mobilizuje ekstracelularne supstance i/ili menja isporuku supstrata tokom fizičkih aktivnosti. Dodatno, [[osteoblast]]i izlučuju IL-6 da bi stimulisali formiranje [[osteoklast]]a. [[Ćelije glatkih mišića]] u [[tunica media|''tunica media'']] mnogih krvnih sudova takođe proizvode IL-6 kao proinflamatorni [[citokin]]. Uloga IL-6 citokina kao antiinflamatornog agenta je posredovana putem njegovih inhibitornih efekata na [[TNF-alfa]] i [[Interleukin 1|IL-1]], i aktivaciju [[Interleukin receptor 1 alfa|IL-1Ra]] i [[Interleukin 1|IL-10]].

== Funkcija ==

IL-6 je jedan od najvažnijih posrednika [[groznica|groznice]] i [[proteini akutne faze|akutne faze odziva]]. On ima sposobnost prolaženja kroz [[krvno-moždana barijera|krvno-moždanu barijeru]] i iniciranja [[PGE2]] sinteze u [[hipotalamus]]u, čime se menja temperatura tela. IL-6 mogu izlučiti [[makrofag]]e u odgovoru na specifične mikrobne molekule, što se naziva [[patogen]] asocirani molekulski obrazac ([[PAMO]]). PAMO molekuli se vezuju za veoma važnu grupu detekcionih molekula [[urođeni imunski sistem|urođenog imunskog sistema]], zvanih receptori prepoznavanja obrazaca ([[RPO]]), među kojima su i [[Toll-like receptor|TLR]] receptori. Oni su prisutni na ćelijskoj površini i intracelularnim kompartmanima, i oni indukuju intracelularne signalne kaskade koje dovode do produkcije inflamatornih citokina. IL-6 je isto tako esencijalan za razvoj [[hibridoma]], i nalazi se u mnogim suplementarnim medijumima za kloniranje kao što je [[BriClone|BriClone<sup>®</sup>]]. IL-6 inhibitori (uključujući [[estrogen]]) se koriste u tretmanu postmenopozne [[osteoporoza|osteoporoze]]. IL-6 isto proizvode [[adipociti]], i za to se misli da je razlog povišenog [[CRP]] nivoa kod gojaznih osoba. U jednog studiji iz [[2009]]. godine sa intranazalno administriranim IL-6, pokazano je da on poboljšava san-asociranu [[konsolidacija memorije|konsolidaciju]] emotivnih memorija.<ref>{{cite journal | title=Enhancing influence of intranasal IL-6 on slow-wave activity and memory consolidation during sleep | journal=Federation of American Societies for Experimental Biology last=Benedict | year=2009 | volume=23 | pages=3629–3636 | doi=10.1096/fj.08-122853 | pmid=19546306}}</ref>

== Receptor ==

IL-6 signalizira kroz receptore na ćelijskoj površini. IL-6 receptor je [[tip I citokin receptor]]ski kompleks koji se sastoji od [[ligand (biohemija)|ligand]]-vezujućeg IL-6Rα lanca ([[klaster diferencijacije|CD126]]), i signal-prenoseće komponente [[gp130]] (isto poznate kao CD130). CD130 je zajednički signal prenosilac za nekoliko citokina među kojima su [[Inhibitorni faktor leukemije]] (LIF), [[cilijarni neurotrofni faktor]], [[onkostatin M]], [[interleukin 11|IL-11]] i [[kardiotrofin 1]], i on je skoro sveprisutno izražen u većini tkiva, dok je CD126 izražavanje ograničeno na određena tkiva. IL-6 interakcija sa njegovim receptorom, podstiče gp130 i IL-6R [[protein]]e da formiraju kompleks, čime se aktivira receptor. Ovi kompleksi približavaju [[intracelularni|intracelularne]] gp130 regione čime se inicira kaskada prenosa signala kroz određene [[transkripcioni faktori|transkripcione faktore]], Janus kinaze ([[JAK]]s) i [[CTAT]] faktore.<ref>{{cite journal | author= Heinrich PC, Behrmann, I, Müller-Newen G, Schaper F, Graeve L | title=Interleukin-6 type cytokine signalling through the gp130(Jak/STAT pathway| journal= Biochem. J. | year= 1998 | volume= 334 | pages= 297–314 | pmid=9716487}}</ref>


IL-6 je verovatno najbolje studiran od svih citokina koji koriste gp130 u njihovim signalnim kompleksima. Drugi citokini koji prenose signal kroz receptor koji sadrži gp130 su [[Interleukin 11]] (IL-11), [[Interleukin 27]] (IL-27), [[cilijarni neurotrofni faktor]] (CNTF), [[kardiotrofin 1]] (CT-1), [[CLCF1|kardiotrofin--sličan citokin]] (CLC), [[Inhibitorni faktor leukemije]] (LIF), [[onkostatin M]] (OSM), [[Kapošijev sarkom-asocirani herpesvirus]] interleukinu 6 sličan [[protein]] ([[KSHV-IL6]]).<ref>{{cite journal | author= Kishimoto T, Akira S, Narazaki M, Taga T | title=Interleukin-6 family of cytokines and gp130 | journal= Blood | year= 1995 | volume= 86 | pages= 1243–1254}}</ref> Ovi citokini se normalno zovu ''IL-6 slični'' ili ''gp130 koristeći'' citokini.<ref>{{cite journal | author= Heinrich PC, Behrmann I, Haan, S, Hermanns, HM, Müller-Newen G, Schaper, F | title=Principles of interleukin-6-type cytokine signalling and its regulation | journal= Biochem. J. | year= 2003 | volume= 374 | pages= 1–20 | pmid=12773095 | doi=10.1042/BJ20030407}}</ref>

Pored receptora vezanih za membranu, rastvorni oblik IL-6R ([[sIL-6R]]) je bio prečišćen iz ljudskog seruma i urina. Mnoge nervne ćelije su neodzivne na stimulaciju samo sa IL-6, ali njihova [[ćelijska deoba|diferencijacija]] i opstanak može biti posredovan kroz sIL-6R akcije. sIL-6R/IL-6 kompleks može da stimuliše izlazak neurita i da pomogne opstanku neurona, i iz tih razloga može biti važna za regeneraciju nerva putem remijelinacije.

== Interakcije ==
Za interleukin 6 je bilo pokazano da formira [[protein-protein interakcija|interakciju]] sa [[interleukin-6 receptor]]om<ref name="pmid14557255">{{cite journal | author = Schwantner A, Dingley AJ, Ozbek S, Rose-John S, Grötzinger J | title = Direct determination of the interleukin-6 binding epitope of the interleukin-6 receptor by NMR spectroscopy | journal = J. Biol. Chem. | volume = 279 | issue = 1 | pages = 571–6 | year = 2004 | month = January | pmid = 14557255 | doi = 10.1074/jbc.M311019200 | url = | issn = }}</ref><ref name="pmid12643274">{{cite journal | author = Schuster B, Kovaleva M, Sun Y, Regenhard P, Matthews V, Grötzinger J, Rose-John S, Kallen KJ | title = Signaling of human ciliary neurotrophic factor (CNTF) revisited. The interleukin-6 receptor can serve as an alpha-receptor for CTNF | journal = J. Biol. Chem. | volume = 278 | issue = 11 | pages = 9528–35 | year = 2003 | month = March | pmid = 12643274 | doi = | url = | issn = }}</ref><ref name="pmid2788034">{{cite journal | author = Taga T, Hibi M, Hirata Y, Yamasaki K, Yasukawa K, Matsuda T, Hirano T, Kishimoto T | title = Interleukin-6 triggers the association of its receptor with a possible signal transducer, gp130 | journal = Cell | volume = 58 | issue = 3 | pages = 573–81 | year = 1989 | month = August | pmid = 2788034 | doi = | url = | issn = }}</ref> u [[glikoprotein 130|glikoproteinom 130]].<ref name="pmid15989626">{{cite journal | author = Kallen KJ, zum Büschenfelde KH, Rose-John S | title = The therapeutic potential of interleukin-6 hyperagonists and antagonists | journal = Expert Opin Investig Drugs | volume = 6 | issue = 3 | pages = 237–66 | year = 1997 | month = March | pmid = 15989626 | doi = 10.1517/13543784.6.3.237 | url = | issn = }}</ref>

== Uloga kod bolesti ==

IL-6 je relevantan u mnogim procesima bolesti kao što su [[Šećerna bolest|dijabetis]],<ref name="pmid16306329">{{cite journal | author = Kristiansen OP, Mandrup-Poulsen T | title = Interleukin-6 and diabetes: the good, the bad, or the indifferent? | journal = Diabetes | volume = 54 Suppl 2 | issue = | pages = S114–24 | year = 2005 | month = December | pmid = 16306329 | doi = | url = | issn = }}</ref> [[ateroskleroza]],<ref name="pmid17684929">{{cite journal | author = Dubiński A, Zdrojewicz Z | title = [The role of interleukin-6 in development and progression of atherosclerosis] | language = Polish | journal = Pol. Merkur. Lekarski | volume = 22 | issue = 130 | pages = 291–4 | year = 2007 | month = April | pmid = 17684929 | doi = | url = | issn = }}</ref> [[lupus]],<ref name="pmid15230289">{{cite journal | author = Tackey E, Lipsky PE, Illei GG | title = Rationale for interleukin-6 blockade in systemic lupus erythematosus | journal = Lupus | volume = 13 | issue = 5 | pages = 339–43 | year = 2004 | pmid = 15230289 | pmc = 2014821 | doi = | url = | issn = }}</ref> [[rak prostate]],<ref name="pmid11312117">{{cite journal | author = Smith PC, Hobisch A, Lin DL, Culig Z, Keller ET | title = Interleukin-6 and prostate cancer progression | journal = Cytokine Growth Factor Rev. | volume = 12 | issue = 1 | pages = 33–40 | year = 2001 | month = March | pmid = 11312117 | doi = | url = | issn = }}</ref> i [[reumatoidni artritis]].<ref name="pmid16582692">{{cite journal | author = Nishimoto N | title = Interleukin-6 in rheumatoid arthritis | journal = Curr Opin Rheumatol | volume = 18 | issue = 3 | pages = 277–81 | year = 2006 | month = May | pmid = 16582692 | doi = 10.1097/01.bor.0000218949.19860.d1 | url = | issn = }}</ref>
Pacijenti sa naprednim/[[metastatički tumor|metastatičkim tumorom]] imaju povišene IL-6 nivoe u krvi.<ref name="urlMedscape.com Log In">{{cite web | url = http://www.medscape.com/viewarticle/537309 | title =  Cancer Patients Typically Have Increased Interleukin-6 Levels | author = | authorlink = | coauthors = | date = 26. 6. 2006. | format = | work = American Society of Clinical Oncology 2006 Annual Meeting, Abstracts 8632 and 8633 | publisher = Medscape.com | pages = | language = | archiveurl = | archivedate = | quote = | accessdate = }}</ref>
Iz ovih razloga postoji interest za razvijanje [[anti-IL-6]] agenata kao terapija protiv većine od ovih bolesti.<ref name="pmid16083340">{{cite journal | author = Barton BE | title = Interleukin-6 and new strategies for the treatment of cancer, hyperproliferative diseases and paraneoplastic syndromes | journal = Expert Opin. Ther. Targets | volume = 9 | issue = 4 | pages = 737–52 | year = 2005 | month = August | pmid = 16083340 | doi = 10.1517/14728222.9.4.737 | url = | issn = }}</ref><ref name="pmid16899109">{{cite journal | author = Smolen JS, Maini RN | title = Interleukin-6: a new therapeutic target | journal = Arthritis Res. Ther. | volume = 8 Suppl 2 | issue = | pages = S5 | year = 2006 | pmid = 16899109 | doi = 10.1186/ar1969 | url = | issn = }}</ref> Prva takva terapija je [[tocilizumab]] koji je odobren za [[reumatoidni artritis]]. [[ALD518]] je u kliničkim ispitivanjima.

== Reference ==
{{reflist|2}}

== Literatura ==
{{refbegin | 2}}
{{PBB_Further_reading 
| citations = 
*{{cite journal  | author=De Kloet ER, Oitzl MS, Schöbitz B |title=Cytokines and the brain corticosteroid receptor balance: relevance to pathophysiology of neuroendocrine-immune communication | url=https://archive.org/details/sim_psychoneuroendocrinology_1994_19_2/page/121 |journal=Psychoneuroendocrinology |volume=19 |issue= 2 |pages= 121–34 |year= 1994 |pmid= 8190832 |doi=10.1016/0306-4530(94)90002-7}}
*{{cite journal  | author=Morishita R, Aoki M, Yo Y, Ogihara T |title=Hepatocyte growth factor as cardiovascular hormone: role of HGF in the pathogenesis of cardiovascular disease |journal=Endocr. J. |volume=49 |issue= 3 |pages= 273–84 |year= 2003 |pmid= 12201209 |doi=10.1507/endocrj.49.273}}
*{{cite journal  | author=Ishihara K, Hirano T |title=IL-6 in autoimmune disease and chronic inflammatory proliferative disease |journal=Cytokine Growth Factor Rev. |volume=13 |issue= 4-5 |pages= 357–68 |year= 2003 |pmid= 12220549 |doi=10.1016/S1359-6101(02)00027-8}}
*{{cite journal  | author=Culig Z, Bartsch G, Hobisch A |title=Interleukin-6 regulates androgen receptor activity and prostate cancer cell growth |journal=Mol. Cell. Endocrinol. |volume=197 |issue= 1-2 |pages= 231–8 |year= 2003 |pmid= 12431817 |doi=10.1016/S0303-7207(02)00263-0}}
*{{cite journal  | author=Rattazzi M, Puato M, Faggin E, ''et al.'' |title=C-reactive protein and interleukin-6 in '''vascular disease''': culprits or passive bystanders? |journal=J. Hypertens. |volume=21 |issue= 10 |pages= 1787–803 |year= 2004 |pmid= 14508181 |doi= 10.1097/01.hjh.0000084735.53355.44}}

*{{cite journal  | author=Berger FG |title=The interleukin-6 gene: a susceptibility factor that may contribute to racial and ethnic disparities in '''breast cancer''' mortality |journal=Breast Cancer Res. Treat. |volume=88 |issue= 3 |pages= 281–5 |year= 2005 |pmid= 15609131 |doi= 10.1007/s10549-004-0726-0 }}
*{{cite journal  | author=Stenvinkel P, Ketteler M, Johnson RJ, ''et al.'' |title=IL-10, IL-6, and TNF-alpha: central factors in the altered cytokine network of uremia--the good, the bad, and the ugly | url=https://archive.org/details/sim_kidney-international_2005-04_67_4/page/1216 |journal=Kidney Int. |volume=67 |issue= 4 |pages= 1216–33 |year= 2005 |pmid= 15780075 |doi= 10.1111/j.1523-1755.2005.00200.x }}
*{{cite journal  | author=Vgontzas AN, Bixler EO, Lin HM, ''et al.'' |title=IL-6 and its circadian secretion in humans |journal=Neuroimmunomodulation |volume=12 |issue= 3 |pages= 131–40 |year= 2005 |pmid= 15905620 |doi= 10.1159/000084844 }}
*{{cite journal  | author=Jones SA |title=Directing transition from innate to acquired immunity: defining a role for IL-6 |journal=J. Immunol. |volume=175 |issue= 6 |pages= 3463–8 |year= 2005 |pmid= 16148087 |doi=}}

*{{cite journal  | author=Copeland KF |title=Modulation of HIV-1 transcription by cytokines and chemokines |journal=Mini reviews in medicinal chemistry |volume=5 |issue= 12 |pages= 1093–101 |year= 2006 |pmid= 16375755 |doi=10.2174/138955705774933383}}
*{{cite journal  | author=Mastorakos G, Ilias I |title=Interleukin-6: a cytokine and/or a major modulator of the response to somatic stress |journal=Ann. N. Y. Acad. Sci. |volume=1088 |issue=  |pages= 373–81 |year= 2007 |pmid= 17192581 |doi= 10.1196/annals.1366.021 }}

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== Spoljašnje veze ==
* {{MeshName|Interleukin-6}}
{{Commons category-inline|Cytokines}}
* [http://www.cancerindex.org/geneweb/IL6.htm IL-6 izražavanje u različitim vrstama raka]
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{{PDB Galerija|geneid=3569}}
{{Interleukini}}
{{Citokini}}

[[Kategorija:Interleukini]]
[[Kategorija:Imunologija]]