Download PDF
CC BY-NC-ND 4.0 · Eur J Dent 2020; 14(03): 483-495
DOI: 10.1055/s-0040-1712718
Review Article

Cytokines and Chemokines in Periodontitis

Doaa Elsayed Ramadan
1   Dental Health Science Postgraduate Program, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
,
Ninuk Hariyani
1   Dental Health Science Postgraduate Program, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
2   Department of Dental Public Health, Faculty of Dental Medicine, Universitas Airlangga, Indonesia
,
Retno Indrawati
1   Dental Health Science Postgraduate Program, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
,
Rini Devijanti Ridwan
1   Dental Health Science Postgraduate Program, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
,
Indeswati Diyatri
1   Dental Health Science Postgraduate Program, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
› Author Affiliations
› Further Information
   Permissions and Reprints

Abstract

Periodontitis is a common inflammatory periodontal disease affecting a wide range of population all over the world. The causing bacteria releases chemicals which activate the innate immune system to release proinflammatory cytokines contributing to more progression. This activates the acquired immune system leading to more progression of periodontitis. As the immune response goes on, released cytokines and chemokines can damage the periodontal ligaments, gingiva, and alveolar bone. There are many types of cytokines and chemokines in periodontitis. Cytokines are peptide mediators who are responsible for cell signaling and communication. Chemokines are a large subfamily of cytokines having the ability to coordinate leukocyte recruitment and activation. This paper is a narrative review of the literature.This review ensures that inflammatory mediators in the case of periodontitis can cause a noticeable damage in the whole apparatus of the periodontium. It causes soft tissue inflammation and bone damage affected by the mediators of both innate and acquired immune system.The inflammatory process is accompanied by large network of cytokines and chemokines. There is high expression of proinflammatory cytokines such as interleukin (IL)-1α, IL-1β, IL-6, IL-12, tumor necrosis factor (TNF)-α, and regulatory cytokines such as IL-4, IL-1(RA) receptor antagonist, IL-10, and induced protein (IP)-10. There is also increased production of cytokines IL-10, IL-12, interferon-γ, IP-10, IL-1RA, and IL-4. Cytokines IL-17, IL-6, IL-1β, TNF-α, macrophage colony-stimulating factor, and prostaglandin E2 trigger the osteoclast activity causing bone resorption.

Keywords

periodontitis - inflammation - mediators - cytokines - chemokines


Publication History

Article published online:
23 June 2020

© .

Thieme Medical and Scientific Publishers Private Ltd.
A-12, Second Floor, Sector -2, NOIDA -201301, India

 

  • References

  • 1 Newman MG. et al. Carranza’s Clinical Periodontology. Elsevier Health Sciences; 2011: 1305-7456
    Google Scholar
  • 2 Pihlstrom BL, Michalowicz BS, Johnson NW. Periodontal diseases. Lancet 2005; 366 (9499) 1809-1820
    CrossrefPubMedGoogle Scholar
  • 3 Graves D. Cytokines that promote periodontal tissue destruction. J Periodontol 2008; 79 (8, Suppl) 1585-1591
    CrossrefPubMedGoogle Scholar
  • 4 Heidari Z, Moudi B, Mahmoudzadeh-Sagheb H. Immunomodulatory factors gene polymorphisms in chronic periodontitis: an overview. BMC Oral Health 2019; 19 (01) 29
    CrossrefPubMedGoogle Scholar
  • 5 Buduneli N, Kinane DF. Host-derived diagnostic markers related to soft tissue destruction and bone degradation in periodontitis. J Clin Periodontol 2011; 38 (Suppl 11) 85-105
    CrossrefPubMedGoogle Scholar
  • 6 Hasan A, Palmer RM. A clinical guide to periodontology: pathology of periodontal disease. Br Dent J 2014; 216 (08) 457-461
    CrossrefPubMedGoogle Scholar
  • 7 Andrukhov O, Ulm C, Reischl H, Nguyen PQ, Matejka M, Rausch-Fan X. Serum cytokine levels in periodontitis patients in relation to the bacterial load. J Periodontol 2011; 82 (06) 885-892
    CrossrefPubMedGoogle Scholar
  • 8 Gemmell E, Marshall RI, Seymour GJ. Cytokines and prostaglandins in immune homeostasis and tissue destruction in periodontal disease. Periodontol 2000 1997; 14 (01) 112-143
    CrossrefPubMedGoogle Scholar
  • 9 Di Benedetto A, Gigante I, Colucci S, Grano M. Periodontal disease: linking the primary inflammation to bone loss. Clin Dev Immunol 2013; 2013: 503754
    CrossrefPubMedGoogle Scholar
  • 10 Tisoncik JR, Korth MJ, Simmons CP, Farrar J, Martin TR, Katze MG. Into the eye of the cytokine storm. Microbiol Mol Biol Rev 2012; 76 (01) 16-32
    CrossrefPubMedGoogle Scholar
  • 11 Kleiner G, Marcuzzi A, Zanin V, Monasta L, Zauli G. Cytokine levels in the serum of healthy subjects. Mediators Inflamm 2013; 2013: 434010
    CrossrefPubMedGoogle Scholar
  • 12 Bonecchi R, Galliera E, Borroni EM, Corsi MM, Locati M, Mantovani A. Chemokines and chemokine receptors: an overview. Front Biosci 2009; 14 (01) 540-551
    CrossrefGoogle Scholar
  • 13 Armitage GC, Cullinan MP. Comparison of the clinical features of chronic and aggressive periodontitis. Periodontol 2000 2010; 53 (01) 12-27
    CrossrefPubMedGoogle Scholar
  • 14 Socransky SS, Haffajee AD, Cugini MA. Smith C, Kent RL Jr. Microbial complexes in subgingival plaque. J Clin Periodontol 1998; 25 (02) 134-144
    CrossrefPubMedGoogle Scholar
  • 15 Balashova N, Dhingra A, Boesze-Battaglia K, Lally ET. Aggregatibacter actinomycetemcomitans leukotoxin induces cytosol acidification in LFA-1 expressing immune cells. Mol Oral Microbiol 2016; 31 (01) 106-114
    CrossrefPubMedGoogle Scholar
  • 16 Gölz L, Memmert S, Rath-Deschner B. et al. LPS from P. gingivalis and hypoxia increases oxidative stress in periodontal ligament fibroblasts and contributes to periodontitis. Mediators Inflamm 2014; 2014: 986264
    CrossrefPubMedGoogle Scholar
  • 17 Sorsa T, Mäntylä P, Tervahartiala T, Pussinen PJ, Gamonal J, Hernandez M. P activation in diagnostics of periodontitis and systemic inflammation. J Clin Periodontol 2011; 38 (09) 817-819
    CrossrefPubMedGoogle Scholar
  • 18 Kachlany SC. Aggregatibacter actinomycetemcomitans leukotoxin: from threat to therapy. J Dent Res 2010; 89 (06) 561-570
    CrossrefGoogle Scholar
  • 19 Kapoor U, Sharma G, Juneja M, Nagpal A. Halitosis: current concepts on etiology, diagnosis and management. Eur J Dent 2016; 10 (02) 292-300
    Article in Thieme ConnectPubMedGoogle Scholar
  • 20 Song B, Zhang YL, Chen LJ. et al. The role of toll-like receptors in periodontitis. Oral Dis 2017; 23 (02) 168-180
    CrossrefPubMedGoogle Scholar
  • 21 Zhang Y, Li X. Lipopolysaccharide-regulated production of bone sialoprotein and interleukin-8 in human periodontal ligament fibroblasts: the role of toll-like receptors 2 and 4 and the MAPK pathway. J Periodontal Res 2015; 50 (02) 141-151
    CrossrefPubMedGoogle Scholar
  • 22 Wara-aswapati N, Chayasadom A, Surarit R. et al. Induction of toll-like receptor expression by porphyromonas gingivalis. J Periodontol 2013; 84 (07) 1010-1018
    CrossrefPubMedGoogle Scholar
  • 23 Kawai T, Akira S. Differentiation, TLR signaling. Cell Death 2006; 13 (05) 816
    CrossrefGoogle Scholar
  • 24 Schuch HS, Peres KG, Demarco FF. et al. Effect of life-course family income trajectories on periodontitis: birth cohort study. J Clin Periodontol 2018; 45 (04) 394-403
    CrossrefPubMedGoogle Scholar
  • 25 Lertpimonchai A, Rattanasiri S, Arj-Ong S Vallibhakara, Attia J, Thakkinstian A. The association between oral hygiene and periodontitis: a systematic review and meta-analysis. Int Dent J 2017; 67 (06) 332-343
    CrossrefPubMedGoogle Scholar
  • 26 Ashraf M Nazir, Almas K. Awareness about the effects of tobacco consumption on oral health and the possibility of smoking behavior among male Saudi schoolchildren. Eur J Dent 2017; 11 (01) 29-35
    Article in Thieme ConnectPubMedGoogle Scholar
  • 27 Sakki TK, Knuuttila ML, Vimpari SS, Hartikainen MS. Association of lifestyle with periodontal health. Community Dent Oral Epidemiol 1995; 23 (03) 155-158
    CrossrefPubMedGoogle Scholar
  • 28 Castro MM, Ferreira RO, Fagundes NCF, Almeida APCPSC, Maia LC, Lima RR. Association between psychological stress and periodontitis: a systematic review. Eur J Dent 2020; 14 (01) 171-179
    Article in Thieme ConnectPubMedGoogle Scholar
  • 29 Kim J, Amar S. Periodontal disease and systemic conditions: a bidirectional relationship. Odontology 2006; 94 (01) 10-21
    CrossrefPubMedGoogle Scholar
  • 30 Meyle J, Dommisch H, Groeger S, Giacaman RA, Costalonga M, Herzberg M. The innate host response in caries and periodontitis. J Clin Periodontol 2017; 44 (12) 1215-1225
    CrossrefPubMedGoogle Scholar
  • 31 Kumaresan D, Balasundaram A, Naik VK, Appukuttan DP. Gingival crevicular fluid periostin levels in chronic periodontitis patients following nonsurgical periodontal treatment with low-level laser therapy. Eur J Dent 2016; 10 (04) 546-550
    Article in Thieme ConnectPubMedGoogle Scholar
  • 32 Lindhe J, Lang NP, Karring T. Text Book of Clinical Periodontology and Implant Dentistry. Copenhagen: Munksgaard; 2003
    Google Scholar
  • 33 Cairo F, Nieri M, Gori AM. et al. Markers of systemic inflammation in periodontal patients: chronic versus aggressive periodontitis. An explorative cross-sectional study. Eur J Oral Implantology 2010; 3 (02) 147-153
    Google Scholar
  • 34 Giacaman RA, Asrani AC, Ross KF, Herzberg MC. Cleavage of protease-activated receptors on an immortalized oral epithelial cell line by Porphyromonas gingivalis gingipains. Microbiology 2009; 155 (Pt 10) 3238-3246
    CrossrefGoogle Scholar
  • 35 Beklen A, Hukkanen M, Richardson R, Konttinen YT. Immunohistochemical localization of toll-like receptors 1-10 in periodontitis. Oral Microbiol Immunol 2008; 23 (05) 425-431
    CrossrefPubMedGoogle Scholar
  • 36 Dommisch H, Reinartz M, Backhaus T, Deschner J, Chung W, Jepsen S. Antimicrobial responses of primary gingival cells to Porphyromonas gingivalis. J Clin Periodontol 2012; 39 (10) 913-922
    CrossrefPubMedGoogle Scholar
  • 37 Hosokawa I, Hosokawa Y, Ozaki K, Yumoto H, Nakae H, Matsuo T. Proinflammatory effects of muramyldipeptide on human gingival fibroblasts. J Periodontal Res 2010; 45 (02) 193-199
    CrossrefPubMedGoogle Scholar
  • 38 Baek KJ, Choi Y, Ji S. Gingival fibroblasts from periodontitis patients exhibit inflammatory characteristics in vitro. Arch Oral Biol 2013; 58 (10) 1282-1292
    CrossrefPubMedGoogle Scholar
  • 39 Jung YJ, Choi YJ, An SJ, Lee HR, Jun HK, Choi BK. Tannerella forsythia GroEL induces inflammatory bone resorption and synergizes with interleukin-17. Mol Oral Microbiol 2017; 32 (04) 301-313
    CrossrefPubMedGoogle Scholar
  • 40 Marki A, Esko JD, Pries AR, Ley K. Role of the endothelial surface layer in neutrophil recruitment. J Leukoc Biol 2015; 98 (04) 503-515
    CrossrefPubMedGoogle Scholar
  • 41 White P, Cooper P, Milward M, Chapple I. Differential activation of neutrophil extracellular traps by specific periodontal bacteria. Free Radic Biol Med 2014; 75 (Suppl 1) S53
    CrossrefPubMedGoogle Scholar
  • 42 White PC, Chicca IJ, Cooper PR, Milward MR, Chapple IL. Neutrophil extracellular traps in periodontitis: a web of intrigue. J Dent Res 2016; 95 (01) 26-34
    CrossrefGoogle Scholar
  • 43 Alfakry H, Malle E, Koyani CN, Pussinen PJ, Sorsa T. Neutrophil proteolytic activation cascades: a possible mechanistic link between chronic periodontitis and coronary heart disease. Innate Immun 2016; 22 (01) 85-99
    CrossrefPubMedGoogle Scholar
  • 44 Hajishengallis G, Chavakis T, Hajishengallis E, Lambris JD. Neutrophil homeostasis and inflammation: novel paradigms from studying periodontitis. J Leukoc Biol 2015; 98 (04) 539-548
    CrossrefPubMedGoogle Scholar
  • 45 Hasturk H, Kantarci A. Activation and resolution of periodontal inflammation and its systemic impact. Periodontol 2000 2015; 69 (01) 255-273
    CrossrefPubMedGoogle Scholar
  • 46 Stadler AF, Angst PD, Arce RM, Gomes SC, Oppermann RV, Susin C. Gingival crevicular fluid levels of cytokines/chemokines in chronic periodontitis: a meta-analysis. J Clin Periodontol 2016; 43 (09) 727-745
    CrossrefPubMedGoogle Scholar
  • 47 Ford PJ, Gamonal J, Seymour GJ. Immunological differences and similarities between chronic periodontitis and aggressive periodontitis. Periodontol 2000 2010; 53 (01) 111-123
    CrossrefPubMedGoogle Scholar
  • 48 Turner MD, Nedjai B, Hurst T, Pennington DJ. Cytokines and chemokines: at the crossroads of cell signalling and inflammatory disease. Biochim Biophys Acta 2014; 1843 (11) 2563-2582
    CrossrefPubMedGoogle Scholar
  • 49 Mosmann TR, Sad S. The expanding universe of T-cell subsets: Th1, Th2 and more. Immunol Today 1996; 17 (03) 138-146
    CrossrefPubMedGoogle Scholar
  • 50 Harrington LE, Hatton RD, Mangan PR. et al. Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol 2005; 6 (11) 1123-1132
    CrossrefPubMedGoogle Scholar
  • 51 Araujo-Pires AC, Francisconi CF, Biguetti CC. et al. Simultaneous analysis of T helper subsets (Th1, Th2, Th9, Th17, Th22, Tfh, Tr1 and Tregs) markers expression in periapical lesions reveals multiple cytokine clusters accountable for lesions activity and inactivity status. J Appl Oral Sci 2014; 22 (04) 336-346
    CrossrefPubMedGoogle Scholar
  • 52 Feghali CA, Wright TM. Cytokines in acute and chronic inflammation. Front Biosci 1997; 2 (01) d12-d26
    CrossrefPubMedGoogle Scholar
  • 53 Preshaw PM, Taylor JJ. How has research into cytokine interactions and their role in driving immune responses impacted our understanding of periodontitis. ? J Clin Periodontol 2011; 38 (Suppl. 11) 60-84
    CrossrefPubMedGoogle Scholar
  • 54 Goldbach-Mansky R. Immunology in clinic review series; focus on autoinflammatory diseases: update on monogenic autoinflammatory diseases: the role of interleukin (IL)-1 and an emerging role for cytokines beyond IL-1. Clin Exp Immunol 2012; 167 (03) 391-404
    CrossrefPubMedGoogle Scholar
  • 55 Comerford I, McColl SR. Mini-review series: focus on chemokines. Immunol Cell Biol 2011; 89 (02) 183-184
    CrossrefPubMedGoogle Scholar
  • 56 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 (03) 173-180
    CrossrefPubMedGoogle Scholar
  • 57 Silva TA, Garlet GP, Lara VS. Martins W Jr, Silva JS, Cunha FQ. Differential expression of chemokines and chemokine receptors in inflammatory periapical diseases. Oral Microbiol Immunol 2005; 20 (05) 310-316
    CrossrefPubMedGoogle Scholar
  • 58 Azuma MM, Samuel RO, Gomes-Filho JE, Dezan-Junior E, Cintra LT. The role of IL-6 on apical periodontitis: a systematic review. Int Endod J 2014; 47 (07) 615-621
    CrossrefPubMedGoogle Scholar
  • 59 Wells TN, Power CA, Proudfoot AE. Definition, function and pathophysiological significance of chemokine receptors. Trends Pharmacol Sci 1998; 19 (09) 376-380
    CrossrefPubMedGoogle Scholar
  • 60 de Carvalho Fraga CA, Alves LR, de Sousa AA. et al. Th1 and Th2-like protein balance in human inflammatory radicular cysts and periapical granulomas. J Endod 2013; 39 (04) 453-455
    CrossrefPubMedGoogle Scholar
  • 61 Graves DT, Cochran D. The contribution of interleukin-1 and tumor necrosis factor to periodontal tissue destruction. J Periodontol 2003; 74 (03) 391-401
    CrossrefPubMedGoogle Scholar
  • 62 Cochran DL. Inflammation and bone loss in periodontal disease. J Periodontol 2008; 79 (08) (Suppl) 1569-1576
    CrossrefPubMedGoogle Scholar
  • 63 Lerner UH. Inflammation-induced bone remodeling in periodontal disease and the influence of post-menopausal osteoporosis. J Dent Res 2006; 85 (07) 596-607
    CrossrefPubMedGoogle Scholar
  • 64 Boyle WJ, Simonet WS, Lacey DL. Osteoclast differentiation and activation. Nature 2003; 423 (6937) 337-342
    CrossrefGoogle Scholar
  • 65 Bascones A, Noronha S, Gómez M, Mota P, Gónzalez Moles MA, Villarroel Dorrego M. Tissue destruction in periodontitis: bacteria or cytokines fault?. Quintessence Int 2005; 36 (04) 299-306
    PubMedGoogle Scholar
  • 66 Nakashima T, Kobayashi Y, Yamasaki S. et al. Protein expression and functional difference of membrane-bound and soluble receptor activator of NF-kappaB ligand: modulation of the expression by osteotropic factors and cytokines. Biochem Biophys Res Commun 2000; 275 (03) 768-775
    CrossrefPubMedGoogle Scholar
  • 67 Yucel-Lindberg T, Båge T. Inflammatory mediators in the pathogenesis of periodontitis. Expert Rev Mol Med 2013; 15: e7
    CrossrefPubMedGoogle Scholar
  • 68 Chatterjee D, Kapoor A, Vijay S, Sobti G, Kara D, Thanvi J. Efficacy of locally administered 1.2% rosuvastatin gel in patients with periodontitis: a randomized placebo controlled clinical trial. Eur J Dent 2019; 13 (01) 29-35
    Article in Thieme ConnectPubMedGoogle Scholar