Volume 10, Issue 4 (2024)                   IEM 2024, 10(4): 319-327 | Back to browse issues page


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Abolnezhadian F, Yousefi Avarvand A, Makvandi M, Khosravi A D, Varnaseri M, Alavi S M, et al . Evaluation of Anti-inflammatory Effects of Naproxen on Pro-inflammatory Cytokines in COVID-19 Patients. IEM 2024; 10 (4) :319-327
URL: http://iem.modares.ac.ir/article-4-75376-en.html
1- Department of Pediatrics, Abuzar Children’s Hospital, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
2- Department of Laboratory Sciences, School of Allied Medical Sciences, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran , arshid.yousefi5@gmail.com
3- Infectious and Tropical Diseases Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
4- Department of Infectious, Razi Hospital, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
5- Department of Immunology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
6- Department of Medical Genetics, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
Abstract:   (429 Views)
Background: COVID-19 (coronavirus disease 2019) was declared as a pandemic by the World Health Organization (WHO) in early 2020. The spectrum of clinical symptoms of COVID-19 patients, including asymptomatic and symptomatic cases, includes dry cough, fatigue, fever, shortness of breath, and gastrointestinal symptoms. However, increased immune inflammatory responses to stimuli could result in overproduction of pro-inflammatory cytokines, immunopathological complications, and death in patients with COVID-19. Given the anti-inflammatory effects of naproxen, this study aimed to evaluate the effect of naproxen on IL-1β, TNF-α, IL-6, IFN-γ, and TGF-β in COVID-19 patients.
Materials & Methods: Serum levels of IL-1β, TNF-α, IL-6, IFN-γ, and TGF-β were determined by a commercial ELISA (enzyme linked immunosorbent assay) kit before and after naproxen treatment.
Findings: According to the results, serum levels of IFN-γ and TGF-β cytokines significantly decreased in patients after treatment with naproxen. In addition, naproxen treatment was effective in reducing the serum levels of IL-6 and IL-1β in patients with COVID-19; however, it did not significantly change the serum level of TNF-α.
Conclusion: Overall, the findings demonstrated the effectiveness of naproxen on regulating the serum levels of pro-inflammatory cytokines in COVID-19 patients.
Full-Text [PDF 517 kb]   (75 Downloads)    
Article Type: Original Research | Subject: Virology
Received: 2024/05/30 | Accepted: 2024/09/23 | Published: 2024/12/20

References
1. 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):507-13. [DOI:10.1016/S0140-6736(20)30211-7] [PMID]
2. Zhang W, Zhao Y, Zhang F, Wang Q, Li T, Liu Z, et al. The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): The experience of clinical immunologists from China. Clin Immunol. 2020;214:108393. [DOI:10.1016/j.clim.2020.108393] [PMID] []
3. Shen K, Yang Y, Wang T, Zhao D, Jiang Y, Jin R, et al. Diagnosis, treatment, and prevention of 2019 novel coronavirus infection in children: Experts' consensus statement. World J Pediatr. 2020;16(3):223-31. https://doi.org/10.1007/s12519-020-00344-6 [DOI:10.1007/s12519-020-00343-7]
4. Sun P, Qie S, Liu Z, Ren J, Xi J. Clinical characteristics of 5732 patients with 2019-nCoV infection. Available at SSRN 3539664. 2020:1-30. [DOI:10.2139/ssrn.3539664]
5. Zhang HW, Yu J, Xu HJ, Lei Y, Pu ZH, Dai WC, et al. Corona virus international public health emergencies: Implications for radiology management. Acad Radiol. 2020;27(4):463-7. [DOI:10.1016/j.acra.2020.02.003] [PMID] []
6. Hung IF, To KK, Chan JF, Cheng VC, Liu KS, Tam A, et al. Efficacy of clarithromycin-naproxen-oseltamivir combination in the treatment of patients hospitalized for influenza A (H3N2) infection: An open-label randomized, controlled, phase IIb/III trial. Chest. 2017;151(5):1069-80. [DOI:10.1016/j.chest.2016.11.012] [PMID]
7. Zheng BJ, Chan KW, Lin YP, Zhao GY, Chan C, Zhang HJ, et al. Delayed antiviral plus immunomodulator treatment still reduces mortality in mice infected by high inoculum of influenza A/H5N1 virus. Proc Natl Acad Sci. 2008;105(23):8091-6. [DOI:10.1073/pnas.0711942105] [PMID] []
8. Shanmugaraj B, Siriwattananon K, Wangkanont K, Phoolcharoen W. Perspectives on monoclonal antibody therapy as potential therapeutic intervention for coronavirus disease-19 (COVID-19). Asian Pac J Allergy Immunol. 2020;38(1):10-8.
9. Wu YC, Chen CS, Chan YJ. The outbreak of COVID-19: An overview. J Chin Med Assoc. 2020;83(3):217-20. [DOI:10.1097/JCMA.0000000000000270] [PMID] []
10. Kampf G, Todt D, Pfaender S, Steinmann E. Persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents. J Hosp Infect. 2020;104(3):246-51. [DOI:10.1016/j.jhin.2020.01.022] [PMID] []
11. Lejal N, Tarus B, Bouguyon E, Chenavas S, Bertho N, Delmas B, et al. Structure-based discovery of the novel antiviral properties of naproxen against the nucleoprotein of influenza A virus. Antimicrob Agents Chemother. 2013;57(5):2231-42. [DOI:10.1128/AAC.02335-12] [PMID] []
12. Arabi YM, Deeb AM, Al-Hameed F, Mandourah Y, Almekhlafi GA, Sindi AA, et al. Macrolides in critically ill patients with Middle East respiratory syndrome. Int J Infect Dis. 2019;81:184-90. [DOI:10.1016/j.ijid.2019.01.041] [PMID] []
13. Mani D, Wadhwani A, Krishnamurthy PT. Drug repurposing in antiviral research: A current scenario. J Young Pharm. 2019;11(2):117-21. [DOI:10.5530/jyp.2019.11.26]
14. Russell B, Moss C, Rigg A, Van Hemelrijck M. COVID-19 and treatment with NSAIDs and corticosteroids: Should we be limiting their use in the clinical setting? Ecancermedicalscience. 2020;14:1023. [DOI:10.3332/ecancer.2020.1023]
15. Dmitrieva O, Shilovskiy I, Khaitov M, Grivennikov S. Interleukins 1 and 6 as main mediators of inflammation and cancer. Biochemistry. 2016;81(2):80-90. [DOI:10.1134/S0006297916020024] [PMID]
16. Lewis TC, Metitiri EE, Winer IH, Comstock AT, Goldsmith AM, Ren X, et al. In inner-city children with asthma infected with rhinovirus, viral load correlates with nasal aspirate cytokine expression but not respiratory symptoms. Am J Respir Crit Care Med. 2016:A1080.
17. Nascimento‐Carvalho EC, Vasconcellos ÂG, Clarêncio J, Andrade D, Barral A, Barral‐Netto M, et al. Evolution of cytokines/chemokines in cases with community‐acquired pneumonia and distinct etiologies. Pediatr Pulmonol. 2020;55(1):169-76. [DOI:10.1002/ppul.24533] [PMID]
18. Beltra JC, Decaluwe H. Cytokines and persistent viral infections. Cytokine. 2016;82:4-15. [DOI:10.1016/j.cyto.2016.02.006] [PMID]
19. Glaser L, Coulter PJ, Shields M, Touzelet O, Power UF, Broadbent L. Airway epithelial derived cytokines and chemokines and their role in the immune response to respiratory syncytial virus infection. Pathogens. 2019;8(3):106. [DOI:10.3390/pathogens8030106] [PMID] []
20. Ong PY, Leung DY. Bacterial and viral infections in atopic dermatitis: A comprehensive review. Clin Rev Allergy Immunol. 2016;51(3):329-37. [DOI:10.1007/s12016-016-8548-5] [PMID]
21. Channappanavar R, Perlman S. Pathogenic human coronavirus infections: Causes and consequences of cytokine storm and immunopathology. Semin Immunopathol. 2017;39:529-39. [DOI:10.1007/s00281-017-0629-x] [PMID] []
22. Rojas JM, Avia M, Martín V, Sevilla N. IL-10: A multifunctional cytokine in viral infections. J Immunol Res. 2017;2017(1):6104054. [DOI:10.1155/2017/6104054] [PMID] []
23. Jiang N, Li Y, Shu T, Wang J. Cytokines and inflammation in adipogenesis: An updated review. Front Med. 2019;13:314-29. [DOI:10.1007/s11684-018-0625-0] [PMID]
24. Alosaimi B, Hamed ME, Naeem A, Alsharef AA, AlQahtani SY, AlDosari KM, et al. MERS-CoV infection is associated with downregulation of genes encoding Th1 and Th2 cytokines/chemokines and elevated inflammatory innate immune response in the lower respiratory tract. Cytokine. 2020;126:154895. [DOI:10.1016/j.cyto.2019.154895] [PMID] []
25. Nguyen V, Chen YW, Johnson JD, Paranjpe A. In vivo evaluation of effect of preoperative ibuprofen on proinflammatory mediators in irreversible pulpitis cases. J Endod. 2020;46(9):1210-6. [DOI:10.1016/j.joen.2020.06.009] [PMID]
26. Villalba MC, Ramírez OV, Jiménez MM, Garcia AA, Alfonso JM, Baéz GG, et al. Interferon gamma, TGF-β1, and RANTES expression in upper airway samples from SARS-CoV-2 infected patients. Clin Immunol. 2020;220:108576. [DOI:10.1016/j.clim.2020.108576] [PMID] []
27. Yan Y, Guo TM, Zhu C. Effects of nonsteroidal anti-inflammatory drugs on serum proinflammatory cytokines in the treatment of ankylosing spondylitis. Biochem Cell Biol. 2018;96(4):450-6. [DOI:10.1139/bcb-2017-0267] [PMID]
28. Zhang Y, Liang D, Dong L, Ge X, Xu F, Chen W, et al. Anti-inflammatory effects of novel curcumin analogs in experimental acute lung injury. Respir Res. 2015;16(1):43. [DOI:10.1186/s12931-015-0199-1] [PMID] []
29. Hu ZJ, Xu J, Yin JM, Li L, Hou W, Zhang LL, et al. Lower circulating interferon-gamma is a risk factor for lung fibrosis in COVID-19 patients. Front Immunol. 2020;11:585647. [DOI:10.3389/fimmu.2020.585647] [PMID] []
30. Conti P, Ronconi G, Caraffa A, Gallenga C, Ross R, Frydas I, et al. Induction of pro-inflammatory cytokines (IL-1 and IL-6) and lung inflammation by coronavirus-19 (COVI-19 or SARS-CoV-2): Anti-inflammatory strategies. J Biol Regul Homeost Agents. 2020;34(2):327-31.
31. Masiello P, Novelli M, Beffy P, Menegazzi M. Can hypericum perforatum (SJW) prevent cytokine storm in COVID‐19 patients? Phytother Res. 2020;34(7):1471. [DOI:10.1002/ptr.6764] [PMID] []
32. Yousefifard M, Zali A, Zarghi A, Madani Neishaboori A, Hosseini M, Safari S. Non‐steroidal anti‐inflammatory drugs in management of COVID‐19: A systematic review on current evidence. Int J Clin Pract. 2020;74(9):e13557. [DOI:10.1111/ijcp.13557] []
33. Conforti C, Giuffrida R, Zalaudek I, Di Meo N. Doxycycline, a widely used antibiotic in dermatology with a possible anti‐inflammatory action against IL‐6 in COVID‐19 outbreak. Dermatol Ther. 2020;33(4):e13437. [DOI:10.1111/dth.13437]
34. Del Valle DM, Kim-Schulze S, Huang HH, Beckmann ND, Nirenberg S, Wang B, et al. An inflammatory cytokine signature predicts COVID-19 severity and survival. Nat Med. 2020;26(10):1636-43. [DOI:10.1038/s41591-020-1051-9] [PMID] []
35. Giollo A, Adami G, Gatti D, Idolazzi L, Rossini M. Coronavirus disease 19 (COVID-19) and non-steroidal anti-inflammatory drugs (NSAID). Ann Rheum Dis. 2020;80(2):e13. [DOI:10.1136/annrheumdis-2020-217598] [PMID]
36. Bayrak Degirmenci P, Aksun S, Altin Z, Bilgir F, Arslan I, Colak H, et al. Allergic rhinitis and its relationship with IL-10, IL-17, TGF-β, IFN-γ, IL 22, and IL-35. Dis Markers. 2018;2018;(1):9131432. [DOI:10.1155/2018/9131432] [PMID] []
37. Inandiklioglu N, Akkoc T. Immune responses to SARS-CoV, MERS-CoV, and SARS-CoV-2. Adv Exp Med Biol. 2020;1288:5-12. [DOI:10.1007/5584_2020_549] [PMID]
38. Sadeghi A, Tahmasebi S, Mahmood A, Kuznetsova M, Valizadeh H, Taghizadieh A, et al. Th17 and Treg cells function in SARS‐CoV-2 patients compared with healthy controls. J Cell Physiol. 2020;236(4):2829-39. [DOI:10.1002/jcp.30047] [PMID]
39. Gadotti AC, de Castro Deus M, Telles JP, Wind R, Goes M, Ossoski RG, et al. IFN-γ is an independent risk factor associated with mortality in patients with moderate and severe COVID-19 infection. Virus Res. 2020;289:198171. [DOI:10.1016/j.virusres.2020.198171] [PMID] []
40. Deftereos SG, Giannopoulos G, Vrachatis DA, Siasos GD, Giotaki SG, Gargalianos P, et al. Effect of colchicine vs standard care on cardiac and inflammatory biomarkers and clinical outcomes in patients hospitalized with coronavirus disease 2019: The GRECCO-19 randomized clinical trial. JAMA Netw Open. 2020;3(6):e2013136. [DOI:10.1001/jamanetworkopen.2020.13136] [PMID] []
41. Mikulska M, Nicolini LA, Signori A, Di Biagio A, Sepulcri C, Russo C, et al. Tocilizumab and steroid treatment in patients with COVID-19 pneumonia. PloS One. 2020;15(8):e0237831. [DOI:10.1371/journal.pone.0237831] [PMID] []
42. Luo P, Liu Y, Qiu L, Liu X, Liu D, Li J. Tocilizumab treatment in COVID‐19: A single center experience. J Med Virol. 2020;92(7):814-8. [DOI:10.1002/jmv.25801] [PMID] []
43. Noroozi R, Branicki W, Pyrc K, Łabaj PP, Pośpiech E, Taheri M, et al. Altered cytokine levels and immune responses in patients with SARS-CoV-2 infection and related conditions. Cytokine. 2020;133:155143. [DOI:10.1016/j.cyto.2020.155143] [PMID] []
44. Polidoro RB, Hagan RS, de Santis Santiago R, Schmidt NW. Overview: Systemic inflammatory response derived from lung injury caused by SARS-CoV-2 infection explains severe outcomes in COVID-19. Front Immunol. 2020;11:1626. [DOI:10.3389/fimmu.2020.01626] [PMID] []

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