Dental Hypotheses

ORIGINAL HYPOTHESIS
Year
: 2021  |  Volume : 12  |  Issue : 1  |  Page : 36--38

Cytokine Profiles in Periodontitis and COVID-19


Farhad Hajizadeh1, Behzad Houshmand1, Mehdi Ekhlasmandkermani1, Saber Khazaei2, Aida Kheiri3,  
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

Correspondence Address:
Behzad Houshmand
Department of Periodontics, School of Dentistry, Shahid Beheshti University of Medical Sciences, Daneshjou Boulevard, Evin, Tehran
Iran

Abstract

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.



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;12:36-38


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 2021 May 18 ];12:36-38
Available from: http://www.dentalhypotheses.com/text.asp?2021/12/1/36/310534


Full Text



 Introduction



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



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



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.

Financial support and sponsorship

Nil.

Conflicts of interest

The authors reported no conflicts of interest.

References

1Ragab D, Salah Eldin H, Taeimah M, Khattab R, Salem R. The COVID-19 cytokine storm; what we know so far. Front Immunol 2020;11:1446.
2Pitones-Rubio V, Chávez-Cortez EG, Hurtado-Camarena A, González-Rascón A, Serafín-Higuera N. Is periodontal disease a risk factor for severe COVID-19 illness? Med Hypotheses 2020;144:109969.
3Wiersinga WJ, Rhodes A, Cheng AC, Peacock SJ, Prescott HC. Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease2019 (COVID-19): a review. JAMA. 2020;324:782-93.
4Dhar SK, Vishnupriyan K, Damodar S, Gujar S, Das M. IL-6 and IL-10 as predictors of disease severity in COVID 19 patients: results from meta-analysis and regression. medRxiv. 2020. DOI: https://doi.org/10.1101/2020.08.15.20175844
5Wu D, Yang XO. TH17 responses in cytokine storm of COVID-19: an emerging target of JAK2 inhibitor Fedratinib. J Microbiol Immunol Infect 2020;53:368-70.
6Herrera D, Serrano J, Roldán S, Sanz M. Is the oral cavity relevant in SARS-CoV-2 pandemic? Clin Oral Investig 2020;24:2925-30.
7Castagnoli R, Votto M, Licari A et al. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children and adolescents: a systematic review. JAMA Pediatr. 2020;174:882-9.
8Pan W, Wang Q, Chen Q. The cytokine network involved in the host immune response to periodontitis. Int J Oral Sci 2019;11:1-3.
9Heidari Z, Moudi B, Mahmoudzadeh-Sagheb H. Immunomodulatory factors gene polymorphisms in chronic periodontitis: an overview. BMC Oral Health 2019;19:1-15.
10Mattuella LG, Campagnaro MB, Vargas AE et al. Plasma cytokines levels in aggressive and chronic periodontitis. Acta Odontol Scand 2013;71:683-8.
11Li H, Liu L, Zhang D, Xu J, Dai H, Tang N et al. SARS-CoV-2 and viral sepsis: observations and hypotheses. Lancet 2020;395:1517-20.
12Havemose‐Poulsen A, Sørensen LK, Stoltze K, Bendtzen K, Holmstrup P. Cytokine profiles in peripheral blood and whole blood cell cultures associated with aggressive periodontitis, juvenile idiopathic arthritis, and rheumatoid arthritis. J Periodontol 2005;76:2276-85.
13Braz-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.
14Kuppalli K, Rasmussen AL. A glimpse into the eye of the COVID-19 cytokine storm. EBioMedicine 2020;55:102789.
15Stephens DS, McElrath MJ. COVID-19 and the path to immunity. JAMA 2020;324:1279-81.
16Räisänen 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.
17Cardoso EM, Reis C, Manzanares-Céspedes MC. Chronic periodontitis, inflammatory cytokines, and interrelationship with other chronic diseases. J Postgrad Med 2018;130:98-104.
18Patel J, Sampson V. The role of oral bacteria in COVID-19. Lancet Microbe. 2020;1:e105.
19Deinzer R, Weik U, Kolb Bachofen V, Herforth A. Comparison of experimental gingivitis with persistent gingivitis: differences in clinical parameters and cytokine concentrations. J. Periodontal Res 2007;42:318-24.
20Ramadan DE, Hariyani N, Indrawati R, Ridwan RD, Diyatri I. Cytokines and chemokines in periodontitis. Eur J Dent 2020;14:483.
21Berglundh T, Liljenberg B, Lindhe J. Some cytokine profiles of T helper cells in lesions of advanced periodontitis. J Clin Periodontol 2002;29:705-9.
22Górska 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.
23Ebersole 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.
24Chatzopoulos G, Doufexi AE, Wolff L, Kouvatsi A. Interleukin-6 and interleukin-10 gene polymorphisms and the risk of further periodontal disease progression. Braz Oral Res 2018;32:e11.
25Borilova Linhartova P, Danek Z, Deissova T et al. Interleukin gene variability and periodontal bacteria in patients with generalized aggressive form of periodontitis. Int J Mol Sci 2020;21:4728.