Thursday, 28 July 2022

Systemic inflammation

in this wiki article on systemic inflammation, our work on covid-19, nutrition and inflammation has been referenced [ref 9].

Chronic systemic inflammation (SI) is the result of release of pro-inflammatory cytokines from immune-related cells and the chronic activation of the innate immune system. It can contribute to the development or progression of certain conditions such as cardiovascular diseasecancerdiabetes mellituschronic kidney diseasenon-alcoholic fatty liver diseaseautoimmune and neurodegenerative disorders,[1] and coronary heart disease.[2]


Release of pro-inflammatory cytokines and activation of the innate immune system may be the result of either external (biological or chemical agents) or internal (genetic mutations/variations) factors. The cytokine Interleukin 6 and C-reactive protein are common inflammatory markers used to diagnose systemic inflammation risk.[3] Baseline C-reactive protein levels deviate due to natural genetic variation, but significant increases can result from risk factors such as smoking, obesity, lifestyle, and high blood pressure.[3]

Systemic chronic inflammation increases with age (also known as inflammaging) due to unresolved acute inflammation and an individual's exposome. Age-related systemic chronic inflammation is associated with several cytokines including CXCL9TRAILinterferon gammaCCL11, and CXCL1, and a proposed measurement of chronic systemic inflammation based on these cytokines (iAge) correlates with immunosenescence and predicts risk for cardiovascular diseasefrailty syndrome, and multimorbidity.[4]


It is firmly established that systemic markers for inflammation predict coronary heart disease complications with or without existing heart disease.[2] Inflammation also plays a role in diabetes risk and new research continues to support this conclusion.[5]

Research suggests chronic inflammation plays a major role in COVID-19 morbidity.[6][7] In severe cases, COVID-19 causes a cytokine storm which contributes to excessive and uncontrolled inflammation of organs, particularly respiratory tissues.[8][9] If untreated, this increased inflammation can result in reduced immune response, pneumonia, lymphoid tissue damage, and death.[8] Individuals with abnormal cytokine production, such as those with obesity or systemic chronic inflammation, have poorer health outcomes from COVID-19.[6][7] Elevated cytokine production alters the innate immune response which leads to abnormal T-cell and B-Cell function that decreases control of viral replication and host defense.[6] Anti-viral therapeutic drugs which also reduce inflammation seem to be the most effective treatment, but research is still ongoing.[9] Reactive oxygen species are upregulated during inflammation as part of the immune response to defend against pathogens.[10] However, excessive inflammation causes dangerous levels of reactive oxygen species which cause oxidative stress to tissues.[10] The immune system naturally produces antioxidant compounds to regulate and detoxify reactive oxygen species.[10] Anti-oxidative therapy with supplements such as Vitamin CVitamin ECurcumin, or Baicalin is speculated to reduce infection severity in COVID-19,[11][9] but previous research has not found antioxidants supplementation to be effective in the prevention of other diseases.[12] Shifting from the typical western diet to a Mediterranean diet or plant-based diet may improve COVID-19 health outcomes by reducing prevalence of comorbidities (i.e. obesity or hypertension), decreasing intake of pro-inflammatory foods, and increasing consumption of anti-inflammatory and antioxidant nutrients.[9][13][14]


While SI may be induced by multiple external factors, research suggests that a lack of control by tolerogenic dendritic cells and T-regulatory cells (Treg) is possibly the primary risk factor for the development of SI. In functioning immune responses, T-helper and T-cytotoxic cells are activated by presentation of antigens by antigen-presenting cells (APCs). Chief among these are dendritic cells (DCs). When a DC presents an antigen to a Treg cell, a signal is then sent to the nucleus of the DC, resulting in the production of Indoleamine 2,3- Dioxygenase (IDO). IDO inhibits T cell responses by depleting tryptophan and producing kynurenine, which is toxic to the cell.

Individuals susceptible to developing chronic systemic inflammation appear to lack proper functioning of Treg cells and TDCs. In these individuals, a lack of control of inflammatory processes results in multiple chemical and food intolerances, autoimmune diseases.


  1. ^ Furman, David; Campisi, Judith; Verdin, Eric; Carrera-Bastos, Pedro; Targ, Sasha; Franceschi, Claudio; Ferrucci, Luigi; Gilroy, Derek W.; Fasano, Alessio; Miller, Gary W.; Miller, Andrew H. (December 2019). "Chronic inflammation in the etiology of disease across the life span"Nature Medicine25 (12): 1822–1832. doi:10.1038/s41591-019-0675-0ISSN 1546-170XPMC 7147972PMID 31806905.
  2. Jump up to:a b Sattar N, McCarey DW, Capell H, McInnes IB (December 2003). "Explaining how "high-grade" systemic inflammation accelerates vascular risk in rheumatoid arthritis"Circulation108 (24): 2957–63. doi:10.1161/01.CIR.0000099844.31524.05PMID 14676136.
  3. Jump up to:a b Sproston, Nicola R.; Ashworth, Jason J. (2018-04-13). "Role of C-Reactive Protein at Sites of Inflammation and Infection"Frontiers in Immunology9: 754. doi:10.3389/fimmu.2018.00754ISSN 1664-3224PMC 5908901PMID 29706967.
  4. ^ Sayed, Nazish; Huang, Yingxiang; Nguyen, Khiem; Krejciova-Rajaniemi, Zuzana; Grawe, Anissa P.; Gao, Tianxiang; Tibshirani, Robert; Hastie, Trevor; Alpert, Ayelet; Cui, Lu; Kuznetsova, Tatiana (2021-07-26). "Author Correction: An inflammatory aging clock (iAge) based on deep learning tracks multimorbidity, immunosenescence, frailty and cardiovascular aging"Nature Aging1 (8): 748. doi:10.1038/s43587-021-00102-xISSN 2662-8465.
  5. ^ Tsalamandris, Sotirios; Antonopoulos, Alexios S.; Oikonomou, Evangelos; Papamikroulis, George-Aggelos; Vogiatzi, Georgia; Papaioannou, Spyridon; Deftereos, Spyros; Tousoulis, Dimitris (February 2019). "The Role of Inflammation in Diabetes: Current Concepts and Future Perspectives"European Cardiology Review14 (1): 50–59. doi:10.15420/ecr.2018.33.1ISSN 1758-3756PMC 6523054PMID 31131037.
  6. Jump up to:a b c Chiappetta, Sonja; Sharma, Arya M.; Bottino, Vincenzo; Stier, Christine (May 2020). "COVID-19 and the role of chronic inflammation in patients with obesity"International Journal of Obesity44 (8): 1790–1792. doi:10.1038/s41366-020-0597-4ISSN 1476-5497PMC 7224343PMID 32409680.
  7. Jump up to:a b Yang, Jing; Zheng, Ya; Gou, Xi; Pu, Ke; Chen, Zhaofeng; Guo, Qinghong; Ji, Rui; Wang, Haojia; Wang, Yuping; Zhou, Yongning (May 2020). "Prevalence of comorbidities and its effects in patients infected with SARS-CoV-2: a systematic review and meta-analysis"International Journal of Infectious Diseases94: 91–95. doi:10.1016/j.ijid.2020.03.017ISSN 1201-9712PMC 7194638PMID 32173574.
  8. Jump up to:a b Tang, Yujun; Liu, Jiajia; Zhang, Dingyi; Xu, Zhenghao; Ji, Jinjun; Wen, Chengping (2020-07-10). "Cytokine Storm in COVID-19: The Current Evidence and Treatment Strategies"Frontiers in Immunology11: 1708. doi:10.3389/fimmu.2020.01708ISSN 1664-3224PMC 7365923PMID 32754163.
  9. Jump up to:a b c d Zabetakis, Ioannis; Lordan, Ronan; Norton, Catherine; Tsoupras, Alexandros (2020-05-19). "COVID-19: The Inflammation Link and the Role of Nutrition in Potential Mitigation"Nutrients12 (5): 1466. doi:10.3390/nu12051466ISSN 2072-6643PMC 7284818PMID 32438620.
  10. Jump up to:a b c Mittal, Manish; Siddiqui, Mohammad Rizwan; Tran, Khiem; Reddy, Sekhar P.; Malik, Asrar B. (2014-03-01). "Reactive Oxygen Species in Inflammation and Tissue Injury"Antioxidants & Redox Signaling20 (7): 1126–1167. doi:10.1089/ars.2012.5149ISSN 1523-0864PMC 3929010PMID 23991888.
  11. ^ Wang, Jing-Zhang; Zhang, Rui-Ying; Bai, Jing (2020-08-01). "An anti-oxidative therapy for ameliorating cardiac injuries of critically ill COVID-19-infected patients"International Journal of Cardiology312: 137–138. doi:10.1016/j.ijcard.2020.04.009ISSN 0167-5273PMC 7133895PMID 32321655.
  12. ^ Katsiki, Niki; Manes, Christos (February 2009). "Is there a role for supplemented antioxidants in the prevention of atherosclerosis?"Clinical Nutrition (Edinburgh, Scotland)28 (1): 3–9. doi:10.1016/j.clnu.2008.10.011ISSN 1532-1983PMID 19042058.
  13. ^ Rishi, Praveen; Thakur, Khemraj; Vij, Shania; Rishi, Lavanya; Singh, Aagamjit; Kaur, Indu Pal; Patel, Sanjay K. S.; Lee, Jung-Kul; Kalia, Vipin C. (2020-09-28). "Diet, Gut Microbiota and COVID-19"Indian Journal of Microbiology60 (4): 420–429. doi:10.1007/s12088-020-00908-0ISSN 0046-8991PMC 7521193PMID 33012868.
  14. ^ Di Renzo, Laura; Gualtieri, Paola; Pivari, Francesca; Soldati, Laura; Attinà, Alda; Cinelli, Giulia; Leggeri, Claudia; Caparello, Giovanna; Barrea, Luigi; Scerbo, Francesco; Esposito, Ernesto (2020-06-08). "Eating habits and lifestyle changes during COVID-19 lockdown: an Italian survey"Journal of Translational Medicine18 (1): 229. doi:10.1186/s12967-020-02399-5ISSN 1479-5876PMC 7278251PMID 32513197.

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