Editing Cytokine (section)

==Adverse effects==

Adverse effects of cytokines have been linked to many disease states and conditions ranging from [[schizophrenia]], [[major depression]]<ref name="pmid20015486">{{cite journal | vauthors = Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK, Lanctôt KL | s2cid = 230209 | title = A meta-analysis of cytokines in major depression | journal = Biol. Psychiatry | volume = 67 | issue = 5 | pages = 446–457 | date = March 2010 | pmid = 20015486 | doi = 10.1016/j.biopsych.2009.09.033 }}</ref> and [[Alzheimer's disease]]<ref name="pmid20692646">{{cite journal | vauthors = Swardfager W, Lanctôt K, Rothenburg L, Wong A, Cappell J, Herrmann N | s2cid = 6544784 | title = A meta-analysis of cytokines in Alzheimer's disease | journal = Biol. Psychiatry | volume = 68 | issue = 10 | pages = 930–941 | date = November 2010 | pmid = 20692646 | doi = 10.1016/j.biopsych.2010.06.012  }}</ref> to [[cancer]].<ref name="pmid11239407">{{cite journal | vauthors = Locksley RM, Killeen N, Lenardo MJ | s2cid = 7657797 | title = The TNF and TNF receptor superfamilies: integrating mammalian biology | journal = Cell | volume = 104 | issue = 4 | pages = 487–501 | date = February 2001 | pmid = 11239407 | doi = 10.1016/S0092-8674(01)00237-9 | doi-access = free }}</ref> T regulatory cells ([[Tregs]]) and related-cytokines are effectively engaged in the process of tumor immune escape and functionally inhibit immune response against the tumor. Forkhead box protein 3 ([[Foxp3]]) as a transcription factor is an essential molecular marker of [[Treg]] cells. [[Foxp3]] polymorphism (rs3761548) might be involved in cancer progression like [[gastric cancer]] through influencing [[Tregs]] function and the secretion of immunomodulatory cytokines such as [[Interleukin 10|IL-10]], [[IL-35]], and [[TGF-β]].<ref>{{cite journal | vauthors = Ezzeddini R, Somi MH, Taghikhani M, Moaddab SY, Masnadi Shirazi K, Shirmohammadi M, Eftekharsadat AT, Sadighi Moghaddam B, Salek Farrokhi A | title = Association of Foxp3 rs3761548 polymorphism with cytokines concentration in gastric adenocarcinoma patients | journal = Cytokine | volume = 138 | issue = | pages = 155351 | date = February 2021 | pmid =  33127257 | doi = 10.1016/j.cyto.2020.155351 | s2cid = 226218796 | url = https://www.sciencedirect.com/science/article/pii/S1043466620303677| issn =1043-4666 }}</ref> 
Normal tissue integrity is preserved by feedback interactions between diverse cell types mediated by [[Cell adhesion molecule|adhesion molecules]] and secreted cytokines; disruption of normal feedback mechanisms in cancer threatens tissue integrity.<ref name="pmid26119834">{{cite journal | vauthors = Vlahopoulos SA, Cen O, Hengen N, Agan J, Moschovi M, Critselis E, Adamaki M, Bacopoulou F, Copland JA, Boldogh I, Karin M, Chrousos GP | title = Dynamic aberrant NF-κB spurs tumorigenesis: a new model encompassing the microenvironment | journal = Cytokine Growth Factor Rev. | volume = 26 | issue = 4 | pages = 389–403 | date = August 2015 | pmid = 26119834 | pmc = 4526340 | doi = 10.1016/j.cytogfr.2015.06.001 }}</ref>

Over-secretion of cytokines can trigger a dangerous [[cytokine storm syndrome]]. Cytokine storms may have been the cause of severe adverse events during a clinical trial of [[TGN1412]]. Cytokine storms are also suspected to have been the main cause of death in the [[1918 flu pandemic|1918 "Spanish Flu" pandemic]]. Deaths were weighted more heavily towards people with healthy immune systems, because of their ability to produce stronger immune responses, with dramatic increases in cytokine levels. Another example of cytokine storm is seen in [[acute pancreatitis]]. Cytokines are integral and implicated in all angles of the cascade, resulting in the [[systemic inflammatory response syndrome]] and [[Multi organ dysfunction|multi-organ failure]] associated with this intra-abdominal catastrophe.<ref name="pmid12483260">{{cite journal |vauthors=Makhija R, Kingsnorth AN |title=Cytokine storm in acute pancreatitis |journal=Journal of Hepato-Biliary-Pancreatic Surgery |volume=9 |issue=4 |pages=401–410 |date=2002 |pmid=12483260 |doi=10.1007/s005340200049}}</ref> In the [[COVID-19 pandemic]], some deaths from [[Coronavirus disease 2019|COVID-19]] have been attributable to cytokine release storms.<ref name="covid-1">{{cite web|last1=Cron |first1=Randy |last2=Chatham |first2=W. Winn |url=https://www.vox.com/2020/3/12/21176783/coronavirus-covid-19-deaths-china-treatment-cytokine-storm-syndrome |title=How doctors can potentially significantly reduce the number of deaths from Covid-19| publisher=[[Vox (website)|Vox]] |access-date=14 March 2020|date=12 March 2020}}</ref><ref name="covid-2">{{cite journal |vauthors=Ruan Q, Yang K, Wang W, Jiang L, Song J |title=Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China |journal=Intensive Care Medicine |volume=46 |issue=5 |pages=846–848 |date=May 2020 |pmid=32125452 |pmc=7080116 |doi=10.1007/s00134-020-05991-x}}</ref><ref name="covid-3">{{cite journal |vauthors=Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ |title=COVID-19: consider cytokine storm syndromes and immunosuppression |journal=Lancet |volume=395 |issue=10229 |pages=1033–1034 |date=March 2020 |pmid=32192578 |pmc=7270045 |doi=10.1016/S0140-6736(20)30628-0}}</ref> Current data suggest cytokine storms may be the source of extensive lung tissue damage and dysfunctional coagulation in [[Coronavirus disease 2019|COVID-19]] infections.<ref>{{cite book |vauthors=Cascella M, Rajnik M, Cuomo A |display-authors=et al |title=Features, Evaluation, and Treatment of Coronavirus |publisher=StatPearls Publishing |url=https://www.ncbi.nlm.nih.gov/books/NBK554776 |access-date=4 December 2020|date=4 October 2020 |pmid=32150360}}</ref>