COVID-19'U ANLAMAK: SİTOKİN ETKİSİNİN İMMÜNOPATOJENİK MEKANİZMALARI

Year 2021, Volume: 28 Issue: 4, 687 - 694, 30.12.2021

Elisha Akanbong Alparslan Kadir Devrim , Ali Şenol Tuba Devrim

https://doi.org/10.17343/sdutfd.971047

Abstract

Sitokin salınım sendromu (SSS) veya sitokin fırtınası,
SARS-CoV-2 tarafından başlatılabilen, bağışıklık
sisteminin orantısız tepkisinden kaynaklanan proinflamatuar
sitokinlerin aşırı üretiminin bir sonucudur.
SARS-CoV-2'nin neden olduğu COVID-19, sitokinlerle
korelasyon göstermektedir. SARS-CoV-2, yaygın
dağılım gösteren makrofajlar ve mast hücreleri sayesinde
IL-1 üretimini tetiklemektedir. IL-1 ise, IL-6 ve
TNF-α üretimlerini etkileme eğilimindedir. COVID-19
şiddetinin ilerlemesi, IL-6 gibi bazı sitokin düzeylerini
etkiler. IL-6, SSS oluşumundan başlıca sorumlu olan
sitokindir. SSS, COVID-19 ile ilgili komplikasyonların
ve COVID-19 ile ilişkili ölümlerin ana nedenidir. Bu
zamana kadar literatürde bildirilmiş verilere rağmen,
SARS-CoV-2 ve sitokinler arasındaki ilişki tam olarak
aydınlatılmış değildir. Bu derleme ile söz konusu ilişkinin
irdelenmesi amaçlamıştır. COVID-19 tedavisi sırasında
sitokinlerin hedeflenmesi, hastaların hayatta
kalma oranlarını artırma ve COVID-19 ile ilişkili ölümleri
azaltma potansiyelini taşımaktadır. COVID-19
hastalığında, sitokin salınım mekanizmalarına ve salınan
sitokinlerin etkilerine odaklanılmasının, özellikle
T lenfositler üzerindeki etkilerinin ve IFN-γ üretiminin
irdelenmesinin, hastalığın ölümcül etkilerini azaltmaya
yardımcı olabileceği düşünülmektedir.

Keywords

COVID-19, Sitokinler, Sitokin Salınım Sendromu, Sitokin Fırtınası

Supporting Institution

Çalışmada herhangi bir destek alınmamıştır.

COMPREHENDING COVID-19: IMMUNOPATHOGENIC MECHANISMS OF CYTOKINE ACTION

Abstract

Cytokine release syndrome (CRS) or cytokine storm is
as a result of the excess production of pro-inflammatory
cytokines which is due to the disproportionate response
of the immune system which can be instigated by
SARS-CoV-2. COVID-19 which is caused by SARSCoV-
2 has a correlation with cytokines. SARSCoV-
2 instigates the production of IL-1 by ubiquitous
macrophages and mast cells. IL-1 tends to influence
the production of IL-6 and TNF-α. The progression
of COVID-19 severity influences the level of certain
cytokines such as IL-6. IL-6 is the cytokine chiefly
responsible for the occurrence of CRS. CRS is the
cause of COVID-19-related complications and the
main cause of COVID-19-related deaths. Despite the
data reported in the literature so far, the relationship
between SARS-CoV-2 and cytokines has not been fully
elucidated. The aim of the present review is to examine
the relationship in question. Targeting cytokines during
COVID-19 treatment has the potential to increase
patient survival and reduce COVID-19-related deaths.
It is concluded that focusing on the mechanisms of
cytokine release and the effects of released cytokines,
especially examining the effects on T lymphocytes
and IFN-γ production in COVID-19 disease, may help
reduce the lethal effects of the disease.

Keywords

COVID-19, Cytokines, Cytokine Release Syndrome, Cytokine Storm

References

• 1. Li X, Geng M, Peng Y, Meng L. Lu Sh. Mol immune Pathog diagnosis COVID-19, J Pharm Anal. 2020; 10(2):102–8.
• 2. Darif D, Hammi I, Kihel A, El Idrissi Saik I, Guessous F, Akarid K. The pro-inflammatory cytokines in COVID-19 pathogenesis: What goes wrong? Microb Pathog [Internet]. 2021; 153:104799. Available from: https://www.sciencedirect.com/science/article/ pii/S0882401021000711
• 3. Kunnumakkara AB, Rana V, Parama D, Banik K, Girisa S, Sahu H et al. COVID-19, cytokines, inflammation, and spices: How are they related?. Life sciences. 2021 Feb 16:119201. https://www. sciencedirect.com/science/article/pii/S0024320521001867
• 4. Karabacak P, Kırdemir P. COVID-19 hastalarında akut solunum sıkıntısı sendromu yönetimi. Med J SDU. 2021 (özel sayı- 1): 51-56. DOI: 10.17343/sdutfd.901174.
• 5. Chan JF, Yuan S, Kok KH, To KK, Chu H, Yang J et al. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. The lancet. 2020; 395(10223): 514-23. Available from: https://www.sciencedirect.com/science/article/pii/ S0140673620301549
• 6. Dinarello CA. Impact of basic research on tomorrow’s medicine. Chest. 2000; 118(2): 503–8.
• 7. dos Santos G, Delay L, Yaksh TL, Corr M. Neuraxial Cytokines in Pain States. Front Immunol [Internet]. 2020; 10:3061. Available from: https://www.frontiersin.org/article/10.3389/fimmu. 2019.03061
• 8. Fares J, Cordero A, Kanojia D, Lesniak MS. The Network of Cytokines in Brain Metastases. Cancers (Basel). 2021; 13(1): 142.
• 9. Chauhan P, Nair A, Patidar A, Dandapat J, Sarkar A, Saha B. A primer on cytokines. Cytokine. 2021 Feb; 155458.
• 10. Devrim T, Ekici H, Devrim AK, Sozmen M, Senol A, Bozkurt KM, Duru O. Late effects of cutaneous 3-methylcholanthrene exposure on DNA damage-related pleiotropic growth factors and oxidative stress markers in mice. Bratisl Med J, 2020; 121(5): 325-330.
• 11. Berraondo P, Sanmamed MF, Ochoa MC, Etxeberria I, Aznar MA, Pérez-Gracia JL et al. Cytokines in clinical cancer immunotherapy. British journal of cancer. 2019; 120(1): 6-15.
• 12. Devrim T, Ataç F, Devrim AK, Balcı M. The concomitant use of USP28 and p53 to predict the progression of urothelial carcinoma of the bladder. Pathol Pract. 2020; 216(1): 152774.
• 13. Simpson S, Kaislasuo J, Guller S, Pal L. Thermal stability of cytokines: A review. Cytokine. 2020; 125:154829.
• 14. Katze M. Into the eye of the cytokine storm. Microbiol Mol Biol Rev. 2012; 76(1): 16–32.
• 15. Fares J, Fares MY, Khachfe HH, Salhab HA, Fares Y. Molecular principles of metastasis: a hallmark of cancer revisited. Signal Transduct Target Ther. 2020; 5(1): 1–17.
• 16. Rider P, Carmi Y, Cohen I. Biologics for targeting inflammatory cytokines, clinical uses, and limitations. Int J Cell Biol. 2016; 2016: 9259646.
• 17. Shimabukuro-Vornhagen A, Gödel P, Subklewe M, Stemmler HJ, Schlößer HA, Schlaak M et al. Cytokine release syndrome. Journal for immunotherapy of cancer. 2018; 6(1):1-4.
• 18. Tang X, Wu C, Li X, Song Y, Yao X, Wu X et al. On the origin and continuing evolution of SARS-CoV-2. National Science Review. 2020; 7(6): 1012-23.
• 19. Ye Q, Wang B, Mao J. The pathogenesis and treatment of the `Cytokine Storm' in COVID-19. J Infect. 2020; 80(6): 607-613.
• 20. Mahmud-Al-Rafat A, Asim MM, Taylor-Robinson AW, Majumder A, Muktadir A, Muktadir H et al. A combinational approach to restore cytokine balance and to inhibit virus growth may promote patient recovery in severe COVID-19 cases. Cytokine, 2020; 15:155228.
• 21. Sallenave J-M, Guillot L. Innate immune signaling and proteolytic pathways in the resolution or exacerbation of SARS-CoV-2 in Covid-19: key therapeutic targets? Front Immunol. 2020;11.
• 22. Conti P, Caraffa A, Gallenga CE, Ross R, Kritas SK, Frydas I et al. Coronavirus-19 (SARS-CoV-2) induces acute severe lung inflammation via IL-1 causing cytokine storm in COVID-19: a promising inhibitory strategy. J Biol Regul Homeost Agents. 2020; 34(6): 1971-5.
• 23. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The lancet. 2020; 395(10223): 497-506.
• 24. Ebihara N, Matsuda A, Nakamura S, Matsuda H, Murakami A. Role of the IL-6 classic-and trans-signaling pathways in corneal sterile inflammation and wound healing. Invest Ophthalmol Vis Sci. 2011; 52(12): 8549–57.
• 25. Goncalves C-A, Sesterheim P. Serum amyloid A protein has been undervalued as a biomarker of COVID-19. Diabetes Metab Res Rev. 2020; 26:e3376.
• 26. Mosquera‐Sulbaran JA, Pedreañez A, Carrero Y, Callejas D. C‐reactive protein as an effector molecule in Covid‐19 pathogenesis. Rev Med Virol. 2021; e2221.
• 27. Chatterjee SK, Saha S, Munoz MNM. Molecular Pathogenesis, Immunopathogenesis and Novel Therapeutic Strategy Against COVID-19. Front Mol Biosci [Internet]. 2020; 7:196. Available from: https://www.frontiersin.org/article/10.3389/ fmolb.2020.00196
• 28. Azkur AK, Akdis M, Azkur D, Sokolowska M, van de Veen W, Brüggen MC et al. Immune response to SARS‐CoV‐2 and mechanisms of immunopathological changes in COVID‐19. Allergy. 2020; 75(7): 1564-81.
• 29. Behrens EM, Koretzky GA. Cytokine storm syndrome: Looking toward the precision medicine era. Arthritis Rheumatol. 2017; 69(6): 1135–43.
• 30. Coperchini F, Chiovato L, Croce L, Magri F, Rotondi M. The cytokine storm in COVID-19: An overview of the involvement of the chemokine/chemokine-receptor system. Cytokine Growth Factor Rev. 2020; 53: 25–32.
• 31. Numbers K, Brodaty H. The effects of the COVID-19 pandemic on people with dementia. Nat Rev Neurol. 2021; 1–2.
• 32. Chen G, Wu DI, Guo W, Cao Y, Huang D, Wang H et al. Clinical and immunological features of severe and moderate coronavirus disease 2019. The Journal of clinical investigation. 2020; 130(5): 2620-9.
• 33. Wang F, Hou H, Luo Y, Tang G, Wu S, Huang M et al. The laboratory tests and host immunity of COVID-19 patients with different severity of illness. JCI insight. 2020; 5(10): e137799.
• 34. Hadjadj J, Yatim N, Barnabei L, Corneau A, Boussier J, Smith N et al. Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients. Science. 2020; 369(6504): 718-24.
• 35. Han H, Ma Q, Li C, Liu R, Zhao L, Wang W et al. Profiling serum cytokines in COVID-19 patients reveals IL-6 and IL-10 are disease severity predictors. Emerging microbes & infections. 2020; 9(1): 1123-30.
• 36. Gao Y, Li T, Han M, Li X, Wu D, Xu Y et al. Diagnostic utility of clinical laboratory data determinations for patients with the severe COVID‐19. Journal of medical virology. 2020; 92(7): 791-6.
• 37. Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020; 46(5): 846–8.
• 38. Liu Y, Zhang C, Huang F, Yang Y, Wang F, Yuan J et al. Elevated plasma levels of selective cytokines in COVID-19 patients reflect viral load and lung injury. National Science Review. 2020; 7(6): 1003-11.
• 39. Ryzhakov G, Lai CC, Blazek K, To K, Hussell T, Udalova I. IL- 17 Boosts Proinflammatory Outcome of Antiviral Response in Human Cells. J Immunol [Internet]. 2011; 187(10): 5357–5362. Available from: http://www.jimmunol.org/content/187/10/5357. abstract
• 40. Hou W, Jin Y-H, Kang HS, Kim BS. Interleukin-6 (IL-6) and IL- 17 Synergistically Promote Viral Persistence by Inhibiting Cellular Apoptosis and Cytotoxic T Cell Function. Perlman S, editor. J Virol [Internet]. 2014; 88(15): 8479 LP – 8489. Available from: http://jvi.asm.org/content/88/15/8479.abstract
• 41. Yang AP, Liu J ping, Tao W qiang, Li H ming. The diagnostic and predictive role of NLR, d-NLR and PLR in COVID-19 patients. Int Immunopharmacol [Internet]. 2020; 84: 106504. Available from: https://doi.org/10.1016/j.intimp.2020.106504
• 42. Feng X, Li S, Sun Q, Zhu J, Chen B, Xiong M, et al. Immune- inflammatory parameters in COVID-19 cases: A systematic review and meta-analysis. Front Med. 2020; 7: 1–14.
• 43. Simadibrata DM, Pandhita BAW, Ananta ME, Tango T. Platelet- to-lymphocyte ratio, a novel biomarker to predict the severity of COVID-19 patients: A systematic review and meta- analysis. J Intensive Care Soc. 2020; DOI: https://doi. org/10.1177/1751143720969587
• 44. Kong J, Wang T, Di Z, Shi B, Yu X, Huang C, et al. Analysis of hematological indexes of COVID-19 patients from fever clinics in Suzhou, China. Int J Lab Hematol. 2020; 42(5): e204–6.
• 45. Xu X, Han M, Li T, Sun W, Wang D, Fu B et al. Effective treatment of severe COVID-19 patients with tocilizumab. Proceedings of the National Academy of Sciences. 2020; 117(20): 10970- 5. Available from: http://www.pnas.org/content/117/20/10970. abstract
• 46. Ye Q, Wang B, Mao J. Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID- 19 . The COVID-19 resource centre is hosted on Elsevier Connect , the company ’ s public news and information. J Infect. 2020;(January).
• 47. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y et al. Epidemiological and Clinical Characteristics of 99 Cases of 2019 Novel Coronavirus Pneumonia in Wuhan, China: a descriptive study. Lancet, 2020; 395 (10223): 507-513.