Editing Cytokine (section)

== Classification ==

=== Structural ===
Structural homogeneity has been able to partially distinguish between cytokines that do not demonstrate a considerable degree of redundancy so that they can be classified into four types:

*The four-[[Helix bundle|α-helix bundle]] family ({{InterPro|IPR009079}}): member cytokines have three-dimensional structures with a bundle of four [[alpha helix|α-helices]]. This family, in turn, is divided into three sub-families:
# the [[interleukin 2|IL-2]] subfamily. This is the largest family. It contains several non-immunological cytokines including [[erythropoietin]] (EPO) and [[thrombopoietin]] (TPO).<ref>{{cite journal | vauthors = Leonard WJ | title = Cytokines and immunodeficiency diseases | journal = Nature Reviews. Immunology | volume = 1 | issue = 3 | pages = 200–208 | date = December 2001 | pmid = 11905829 | doi = 10.1038/35105066 | url = https://zenodo.org/record/1233113 | s2cid = 5466985 | doi-access = free }}</ref> They can be grouped into ''long-chain'' and ''short-chain'' cytokines by topology.<ref>{{cite journal | vauthors = Rozwarski DA, Gronenborn AM, Clore GM, Bazan JF, Bohm A, Wlodawer A, Hatada M, Karplus PA | title = Structural comparisons among the short-chain helical cytokines | journal = Structure | volume = 2 | issue = 3 | pages = 159–173 | date = March 1994 | pmid = 8069631 | doi = 10.1016/s0969-2126(00)00018-6 | doi-access = free }}</ref> Some members share the [[common gamma chain]] as part of their receptor.<ref>{{cite journal | vauthors = Reche PA | title = The tertiary structure of γc cytokines dictates receptor sharing | journal = Cytokine | volume = 116 | pages = 161–168 | date = April 2019 | pmid = 30716660 | doi = 10.1016/j.cyto.2019.01.007 | s2cid = 73449371 }}</ref>
# the [[interferon|interferon (IFN)]] subfamily.
# the [[interleukin 10|IL-10]] subfamily.
*The [[interleukin 1|IL-1]] family, which primarily includes IL-1 and [[interleukin|IL-18]].
* The [[cysteine knot]] cytokines ({{UniProt|IPR029034}}) include members of the [[transforming growth factor beta superfamily]], including [[TGF beta 1|TGF-β1]], [[TGF beta 2|TGF-β2]] and [[TGF beta 3|TGF-β3]].
* The [[interleukin 17|IL-17]] family, which has yet to be completely characterized, though member cytokines have a specific effect in promoting proliferation of T-cells that have cytotoxic effects.

=== Functional ===
A classification that proves more useful in clinical and experimental practice outside of [[structural biology]] divides immunological cytokines into those that enhance [[cellular immune response]]s, type 1 (TNFα, IFN-γ, etc.), and those that enhance [[antibody]] responses, type 2 (TGF-β, [[interleukin 4|IL-4]], IL-10, [[interleukin 13|IL-13]], etc.). A key focus of interest has been that cytokines in one of these two sub-sets tend to inhibit the effects of those in the other. Dysregulation of this tendency is under intensive study for its possible role in the [[pathogenesis]] of [[autoimmune disorder]]s. Several [[inflammatory cytokine]]s are induced by [[oxidative stress]].<ref name="pmid10477716">{{cite journal | vauthors = Vlahopoulos S, Boldogh I, Casola A, Brasier AR | title = Nuclear factor-kappaB-dependent induction of interleukin-8 gene expression by tumor necrosis factor alpha: evidence for an antioxidant sensitive activating pathway distinct from nuclear translocation | journal = Blood | volume = 94 | issue = 6 | pages = 1878–1879 | date = September 1999 | pmid = 10477716 | doi = 10.1182/blood.V94.6.1878.418k03_1878_1889 | s2cid = 25974629 }}</ref><ref name="pmid17461946">{{cite journal | vauthors = David F, Farley J, Huang H, Lavoie JP, Laverty S | title = Cytokine and chemokine gene expression of IL-1beta stimulated equine articular chondrocytes | journal = Vet Surg | volume = 36 | issue = 3 | pages = 221–227 | date = April 2007 | pmid = 17461946 | doi = 10.1111/j.1532-950X.2007.00253.x  }}</ref> The fact that cytokines themselves trigger the release of other cytokines<ref name="pmid24185478">{{cite journal | vauthors = Chokkalingam V, Tel J, Wimmers F, Liu X, Semenov S, Thiele J, Figdor CG, Huck WT | title = Probing cellular heterogeneity in cytokine-secreting immune cells using droplet-based microfluidics | journal = Lab Chip | volume = 13 | issue = 24 | pages = 4740–4744 | date = December 2013 | pmid = 24185478 | doi = 10.1039/c3lc50945a | url = http://repository.tue.nl/855231 | access-date = 21 November 2020 | archive-date = 29 November 2020 | archive-url = https://web.archive.org/web/20201129095235/http://repository.tue.nl/855231 | url-status = dead }}</ref><ref name="pmid11922866">{{cite journal | vauthors = Carpenter LR, Moy JN, Roebuck KA | title = Respiratory syncytial virus and TNF alpha induction of chemokine gene expression involves differential activation of Rel A and NF-kappa B1 | journal = BMC Infect. Dis. | volume = 2 | pages = 5 | date = March 2002 | pmid = 11922866 | pmc = 102322 | doi = 10.1186/1471-2334-2-5 | doi-access = free }}</ref><ref name="pmid16191192">{{cite journal | vauthors = Tian B, Nowak DE, Brasier AR | title = A TNF-induced gene expression program under oscillatory NF-kappaB control | journal = BMC Genomics | volume = 6 | pages = 137 | date = September 2005 | pmid = 16191192 | pmc = 1262712 | doi = 10.1186/1471-2164-6-137  | doi-access = free }}</ref> and lead to increased oxidative stress makes them important in chronic [[inflammation]], as well as other immunoresponses, such as fever and acute phase proteins of the liver (IL-1,6,12, IFN-a). Cytokines also play a role in anti-inflammatory pathways and are a possible therapeutic treatment for pathological pain from inflammation or peripheral nerve injury.<ref name="pmid17426506">{{cite journal | vauthors = Zhang JM, An J | title = Cytokines, inflammation, and pain | journal = Int Anesthesiol Clin | volume = 45 | issue = 2 | pages = 27–37 | date = 2007 | pmid = 17426506 | pmc = 2785020 | doi = 10.1097/AIA.0b013e318034194e }}</ref> There are both pro-inflammatory and [[anti-inflammatory]] cytokines that regulate this{{Clarify|reason=Which pathway?|date=July 2024}} pathway.