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 Table of Contents  
Year : 2021  |  Volume : 12  |  Issue : 1  |  Page : 36-38

Cytokine Profiles in Periodontitis and COVID-19

1 Department of Periodontics, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran
2 Department of Endodontics, School of Dentistry, Kermanshah University of Medical Sciences, Kermanshah, Iran
3 Dental Student, Gifted and Talented Dental Students Division, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Date of Submission22-Oct-2020
Date of Decision05-Nov-2020
Date of Acceptance20-Nov-2020
Date of Web Publication2-Mar-2021

Correspondence Address:
Behzad Houshmand
Department of Periodontics, School of Dentistry, Shahid Beheshti University of Medical Sciences, Daneshjou Boulevard, Evin, Tehran
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/denthyp.denthyp_161_20

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Introduction: SARS-CoV-2 is a novel coronavirus that causes an infectious disease named COVID-19. Respiratory distress syndrome and multiple organ failure are the common outcomes of COVID-19 that may finally lead to death. During COVID-19, cytokine storm takes place that is known by the release of notable amounts of pro-inflammatory cytokines including IL-1, IL-6, and TNF-α. The Hypothesis: Periodontal disease are a group of inflammatory diseases in which elevated levels of some cytokine such as IL-1, IL-2, IL-5, IL-6, IL-10, and TNF-α are observed in patients’ serums. Due to the similarity of cytokine expressions in these two diseases, there might be a possible association between COVID-19 and periodontitis, especially the chronic type. Also, genotype polymorphisms of IL-1, IL-6, IL-10, and TNF-α have been proposed to be in association with chronic periodontitis susceptibility. Evaluation of the Hypothesis: assessment of these polymorphisms may also play a significant role in detection of these diseases.

Keywords: Corona virus, COVID-19, cytokine, periodontitis

How to cite this article:
Hajizadeh F, Houshmand B, Ekhlasmandkermani M, Khazaei S, Kheiri A. Cytokine Profiles in Periodontitis and COVID-19. Dent Hypotheses 2021;12:36-8

How to cite this URL:
Hajizadeh F, Houshmand B, Ekhlasmandkermani M, Khazaei S, Kheiri A. Cytokine Profiles in Periodontitis and COVID-19. Dent Hypotheses [serial online] 2021 [cited 2023 Jun 2];12:36-8. Available from:

  Introduction Top

COVID-19 is a new emerged infectious disease caused by a novel coronavirus named SARS-CoV-2 that belongs to the beta-corona virus subfamily.[1],[2] Corona viruses are considered as enveloped viruses that have positive single-stranded large RNA.[1],[3] COVID-19 pandemic has brought a real threat to mankind because it causes acute respiratory distress syndrome (ARDS), not only leads to pulmonary edema and lung failure, but also triggers damage to liver, heart, and kidney.[4],[5] This virus transmits human-to-human, through droplets of coughs and sneezes, or direct contact.[1],[6]

Although a large number of COVID-19 patients are asymptomatic or represent mild symptoms, some of them develop pneumonia, of which about 10% need mechanical ventilation.[1],[2],[7] Dry cough, shortness of breath, fever, fatigue, nausea, vomiting, diarrhea, and headache can be named as the most common symptoms.[1],[3],[6]

Periodontal diseases (PDs) are a subgroup of inflammatory diseases that cause an inflammation in soft tissue, progressive bone loss, and periodontal ligament damage. Through a slow process, gingivitis that is very frequent in population can lead to a destructive condition called “periodontitis.”[8],[9],[10]

  The Hypothesis Top

Periodontal diseases can have an association with COVID-19 illness. In both of these diseases, cytokines have a significant role. So, the similarity of cytokines that are released during different phases of these two diseases may present the possible influence of PD and COVID-19 on one another.

  Evaluation of the Hypothesis Top

Cytokines play an important role in immunopathology of COVID-19,[11] as well as periodontitis.[1],[12] Cytokines are soluble proteins secreted by cells in order to respond against tissue injuries and microbial agents.[13]

COVID-19 is accompanied by the release of a noticeable amount of pro-inflammatory cytokines, better known as “cytokine storm” (CS). Pro-inflammatory cytokines consist of type I, II interferons, IL-1, IL-6, and TNF-α that defend against viral infections during innate immune response.[4] CS is a very serious condition requiring immediate and appropriate intervention.[1],[14] Moreover, several studies reported higher amounts of IL-7, IL-8, IL-9, IL-10 IL-17, G-CSF, MCP-1, IP-10, MIP-1A, and MIPI-B in COVID-19 patients,[1],[5],[11],[14] whereas IL-4, IL-5, and IL-13 did not contribute to acute COVID-19 severity.[15]

Following CS, different immune cells migrate from circulation to the site of infection. Due to the destructive act of these cells, capillary damage, alveolar damage, acute lung injury, multiorgan failure, and ultimately death are potential to take place.[1]

Recent studies presented potential relation between periodontal disease (PD) and COVID-19. The inflammatory reaction during periodontitis could influence the severity and progression of COVID-19.[2],[16],[17] Furthermore, several studies stated this hypothesis as a consequence of bacterial superinfection that can be associated with the oral cavity. Invasion of bacteria pathogens through ulceration of gingival epithelium may also link periodontitis and COVID-19 complications.[6],[16],[18]

Several studies assessed cytokine profiles in periodontal diseases and indicated that in gingivitis, patients had noticeable higher IL-1ß and lower IL-8 concentrations at fourth stage.[19] Increased level of IL-2 and TNF-α and decreased concentration of IL-5 and INF-γ were found in patients with aggressive periodontitis in comparison to healthy people. On the other hand, in patients with chronic periodontitis, amount of IL-1α, IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-10, IL-17, and TNF-α were elevated in serum samples and only INF-γ was dropped.[10],[17],[20] In a study that focused on cytokine profiles of Th-1 and Th-2 cells, it was showed that not only both Th-1 and Th-2 cells had functioned in chronic periodontitis (CP), but also CD4+ cells had showed expression of INF-γ, IL-2, IL-4, and IL-6.[21] Furthermore, it has been shown that there are higher levels of IL-1ß, IL-2, INF-γ, TNF-α, and IL-10 in the serum samples of periodontitis patients.[22] Higher levels of plasma IL-10 and Il-1Ra were also mentioned in another study.[12]

Ebersole et al.[23] showed increased expression of IL-1ß and IL-6 during acute phase of disease as well as a significant upregulation of IL-2 after 5 months. The possible association between IL-1ß, IL-6, and TNF-α and pathogenesis of periodontitis have been also proposed.[8]Furthermore, assessment of susceptible genotypes showed that gene polymorphism can have a great effect on the further risk of PD onset and progression. IL-10rs1800872 polymorphism was proved to be associated with higher stages of PD.[24] Some evidences indicated an association between single nucleotide polymorphisms in IL-1α, IL-1ß, IL-6, IL-10, TNF-α, and INF-γ, and CP susceptibility.[9] Also, IL-10-1087GG genotype and IL-10-GCC haplotype were presented to be a possible risk factor for generalized aggressive periodontitis development.[25]

According to the observations, similarity of serum level change of main cytokine profiles is more evident between COVID-19 and chronic periodontitis than other PDs, suggesting that there can be a possible association between these two diseases. Besides, due to the influence of gene polymorphism of cytokine-related genes including IL-1α, IL-1ß, IL-6, IL-10, TNF-α, and INF-γ on PD, it is possible that it also plays a role in COVID-19. So further studies evaluating the effect of COVID-19 and periodontitis on each other and also influence of different cytokine genotypes are suggested.

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Conflicts of interest

The authors reported no conflicts of interest.

  References Top

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Braz-Silva PH, Bergamini ML, Mardegan AP, De Rosa CS, Hasseus B, Jonasson P. Inflammatory profile of chronic apical periodontitis: a literature review. Acta Odontol Scand 2019;77:173-80.  Back to cited text no. 13
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Stephens DS, McElrath MJ. COVID-19 and the path to immunity. JAMA 2020;324:1279-81.  Back to cited text no. 15
Räisänen IT, Umeizudike KA, Pärnänen P et al. Periodontal disease and targeted prevention using aMMP-8 point-of-care oral fluid analytics in the COVID-19 era. Med Hypotheses 2020;144:110276.  Back to cited text no. 16
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Ramadan DE, Hariyani N, Indrawati R, Ridwan RD, Diyatri I. Cytokines and chemokines in periodontitis. Eur J Dent 2020;14:483.  Back to cited text no. 20
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Górska R, Gregorek H, Kowalski J, Laskus‐Perendyk A, Syczewska M, Madaliński K. Relationship between clinical parameters and cytokine profiles in inflamed gingival tissue and serum samples from patients with chronic periodontitis. J Clin Periodontol 2003;30:1046-52.  Back to cited text no. 22
Ebersole JL, Kirakodu S, Novak MJ et al. Cytokine gene expression profiles during initiation, progression and resolution of periodontitis. J Clin Periodontol 2014;41:853-61.  Back to cited text no. 23
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