Top

Clinical Oral Investigations

Published in:

01-05-2013 | Original Article

Influence of IL-6 haplotypes on clinical and inflammatory response in aggressive periodontitis

Authors: L. Nibali, G. Pelekos, F. D’Aiuto, N. Chaudhary, R. Habeeb, D. Ready, M. Parkar, N. Donos

Published in: Clinical Oral Investigations | Issue 4/2013

Abstract

Objectives

The aim of this study was to investigate the inflammatory response in aggressive periodontitis (AgP) patients after periodontal therapy and associate these changes to subjects’ interleukin-6 (IL-6) genetic variants.

Materials and methods

Twelve non-smoking UK Caucasian patients with AgP were selected based on their IL6 haplotypes (six haplotype positive and six haplotype negative based on polymorphisms rs 2069827 and rs 2069825) and underwent full mouth non-surgical periodontal therapy, followed by open flap surgery. Gingival crevicular fluid (GCF) and peripheral blood samples were taken at baseline and at six different time points after treatment. Gingival biopsy samples were harvested during surgery and underwent immunohistochemical analysis for identification of IL-6.

Results

An overall improvement in clinical periodontal parameters was observed following periodontal therapy. Haplotype status was associated with clinical presentation, Aggregatibacter actinomycetemcomitans counts in subgingival plaque samples, white cell count, neutrophils, red cell count and haemoglobin. GCF IL-6 concentrations increased dramatically 1 day after surgery and IL-6 haplotype-positive subjects exhibited a higher magnitude in this increase.

Conclusions

IL6 haplotypes may have an effect on clinical presentation and magnitude and kinetics of local and systemic inflammatory responses following non-surgical and surgical periodontal therapy in aggressive periodontitis.

Clinical relevance

Detecting IL-6 haplotype-positive periodontitis patients might become helpful in identifying subjects prone to excessive inflammatory response and increased periodontal breakdown.

Ebersole JL, Machen RL, Steffen MJ, Willmann DE (1997) Systemic acute-phase reactants, C-reactive protein and haptoglobin, in adult periodontitis. Clin Exp Immunol 107:347–352PubMedCrossRef

Katz J, Flugelman MY, Goldberg A, Heft M (2002) Association between periodontal pockets and elevated cholesterol and low density lipoprotein cholesterol levels. J Periodontol 73:494–500PubMedCrossRef

D’Aiuto F, Sabbah W, Netuveli G, Donos N, Hingorani AD, Deanfield J, Tsakos G (2008) Association of the metabolic syndrome with severe periodontitis in a large U.S. population-based survey. J Clin Endocrinol Metab 93:3989–94PubMedCrossRef

Lofthus JE, Waki MY, Jolkovsky DL, Otomocorgel J, Newman MG, Flemmig T et al (1991) Bacteremia following subgingival irrigation and scaling and root planing. J Periodontol 62:602–607PubMedCrossRef

Behle JH, Sedaghatfar MH, Demmer RT, Wolf DL, Celenti R, Kebschull M et al (2009) Heterogeneity of systemic inflammatory responses to periodontal therapy. J Clin Periodontol 36:287–294PubMedCrossRef

Loos BG, John RP, Laine ML (2005) Identification of genetic risk factors for periodontitis and possible mechanisms of action. J Clin Periodontol 32:159–179PubMedCrossRef

Nibali L, Donos N, Henderson B (2009) Periodontal infectogenomics. J Med Microbiol 58:1269–74PubMedCrossRef

Bennermo M, Held C, Stemme S, Ericsson CG, Silveira A, Green F et al (2004) Genetic predisposition of the interleukin-6 response to inflammation: implications for a variety of major diseases? Clin Chem 50:2136–2140PubMedCrossRef

Bamoulid J, Courivaud C, Deschamps M, Gaugler B, Tiberghien P, Chalopin JM et al (2011) The interleukin-6 gene promoter polymorphism-174 and atherosclerotic events in overweight transplanted patients. J Transplant 2011:803429PubMed

10.

Poikonen K, Lajunen T, Silvennoinen-Kassinen S, Leinonen M, Saikku P (2009) Effects of CD14, TLR2, TLR4, LPB, and IL-6 gene polymorphisms on Chlamydia pneumoniae growth in human macrophages in vitro. Scand J Immunol 70:34–39PubMedCrossRef

11.

Hirano T, Ishihara K, Hibi M (2000) Roles of STAT3 in mediating the cell growth, differentiation and survival signals relayed through the IL-6 family of cytokine receptors. Oncogene 19:2548–2556PubMedCrossRef

12.

Jones KG, Brull DJ, Brown LC, Sian M, Greenhalgh RM, Humphries SE et al (2001) Interleukin-6 (IL-6) and the prognosis of abdominal aortic aneurysms. Circulation 103:2260–2265PubMedCrossRef

13.

Trevilatto PC, Scarel-Caminaga RM, de Brito RB, de Souza AP, Line SRP (2003) Polymorphism at position-174 of IL-6 gene is associated with susceptibility to chronic periodontitis in a Caucasian Brazilian population. J Clin Periodontol 30:438–442PubMedCrossRef

14.

Nibali L, Ready DR, Parkar M, Brett PM, Wilson M, Tonetti MS et al (2007) Gene polymorphisms and the prevalence of key periodontal pathogens. J Dent Res 86:416–420PubMedCrossRef

15.

D’Aiuto F, Parkar M, Andreou G, Suvan J, Brett PM, Ready D et al (2004) Periodontitis and systemic inflammation: control of the local infection is associated with a reduction in serum inflammatory markers. J Dent Res 83:156–160PubMedCrossRef

16.

Nibali L, D’Aiuto F, Donos N, Griffiths GS, Parkar M, Tonetti MS, Humphries SE, Brett PM (2009) Association between periodontitis and common variants in the promoter of the interleukin-6 gene. Cytokine 45:50–54PubMedCrossRef

17.

Shao MY, Huang P, Cheng R, Hu T (2009) Interleukin-6 polymorphisms modify the risk of periodontitis: a systematic review and meta-analysis. J Zhejiang Univ Sci B 10(12):920–927PubMedCrossRef

18.

Nikolopoulos GK, Dimou NL, Hamodrakas S, Bagos PG (2008) Cytokine gene polymorphisms in periodontal disease: a meta-analysis of 53 studies including 4178 cases and 4590 controls. J Clin Periodontol 35:754–767PubMedCrossRef

19.

Salzberg TN, Overstreet BT, Rogers JD, Califano JV, Best AM, Schenkein HA (2006) C-reactive protein in patients with aggressive periodontitis. J Periodontol 77:933–939PubMedCrossRef

20.

Lang NP, Bartold M, Cullinan M, Mombelli A, Murakami S, Page R et al (1999) Consensus reports: aggressive periodontitis. Ann Periodontol 4:53CrossRef

21.

O’Leary TJ, Drake RB, Naylor JE (1972) The plaque control record. J Periodontol 43:38PubMedCrossRef

22.

Ainamo J, Bay I (1975) Problems and proposals for recording gingivitis and plaque. Int Dent J 25:229–235PubMed

23.

Nibali L, Tonetti MS, Ready D, Parkar M, Brett PM, Donos N, D’Aiuto F (2008) Interleukin-6 polymorphisms are associated with pathogenic bacteria in periodontitis patients. J Periodontol 79:677–683PubMedCrossRef

24.

Fishman D, Faulds G, Jeffery R, Mohamed-Ali V, Yudkin JS, Humphries S et al (1998) The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis. J Clin Invest 102:1369–1376PubMedCrossRef

25.

Fife MS, Ogilvie EM, Kelberman D, Samuel J, Gutierrez A, Humphries SE et al (2005) Novel IL-6 haplotypes and disease association. Genes Immun 6:367–370PubMedCrossRef

26.

Griffiths GS, Curtis MA, Wilton JMA (1988) Selection of A filter-paper with optimum properties for the collection of gingival crevicular fluid. J Periodont Res 23:33–38PubMedCrossRef

27.

Matsuki Y, Yamamoto T, Hara K (1992) Detection of inflammatory cytokine messenger-Rna (Messenger Rna)-expressing cells in human inflamed gingiva by combined in situ hybridization and immunohistochemistry. Immunology 76:42–47PubMed

28.

Lappin DF, Macleod CP, Kerr A, Mitchell T, Kinane DF (2001) Anti-inflammatory cytokine IL-10 and T cell cytokine profile in periodontitis granulation tissue. Clin Exp Immunol 123:294–300PubMedCrossRef

29.

Donati M, Liljenberg B, Padyukov L, Berglundh T (2008) Local expression of interleukin-10 and mCD14 in relation to the -1087 IL-10 and -159 CD14 gene polymorphisms in chronic periodontitis. J Periodontol 79:517–524PubMedCrossRef

30.

Syed SA, Loesche WJ (1972) Survival of human dental plaque flora in various transport media. Appl Microbiol 24:638–44PubMed

31.

Nibali L, Madden I, Chillida FF, Heitz-Mayfield LJA, Brett PM, Donos N (2011) IL6-174 genotype associated with Aggregatibacter actinomycetemcomitans in Indians. Oral Dis 17:232–237PubMedCrossRef

32.

Johanssen A, Rydmark I, Soder B, Asberg M (2007) Gingival inflammation, increased periodontal pocket depth and elevated interleukin-6 in gingival crevicular fluid of depressed women on long-term sick leave. J Periodont Res 42:546–552CrossRef

33.

Cobb CM (2002) Clinical significance of non-surgical periodontal therapy: an evidence-based perspective of scaling and root planing. J Clin Periodontol 29:6–16PubMedCrossRef

34.

Heitz-Mayfield LJ, Trombelli L, Heitz F, Needleman I, Moles D (2002) A systematic review of the effect of surgical debridement vs non-surgical debridement for the treatment of chronic periodontitis. J Clin Periodontol 29(suppl 3):92–102PubMedCrossRef

35.

Tonetti MS, D’Aiuto F, Nibali L, Donald A, Storry C, Parkar M et al (2007) Treatment of periodontitis and endothelial function. N Engl J Med 356:911–920PubMedCrossRef

36.

Graziani F, Cei S, Tonetti M, Paolantonio M, Serio R, Sammartino G et al (2010) Systemic inflammation following non-surgical and surgical periodontal therapy. J Clin Periodontol 37:848–854PubMedCrossRef

Title: Influence of IL-6 haplotypes on clinical and inflammatory response in aggressive periodontitis
Authors: L. Nibali
G. Pelekos
F. D’Aiuto
N. Chaudhary
R. Habeeb
D. Ready
M. Parkar
N. Donos
Publication date: 01-05-2013
Publisher: Springer-Verlag
Published in: Clinical Oral Investigations / Issue 4/2013
Print ISSN: 1432-6981
Electronic ISSN: 1436-3771
DOI: https://doi.org/10.1007/s00784-012-0804-3

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Influence of IL-6 haplotypes on clinical and inflammatory response in aggressive periodontitis

Abstract

Objectives

Materials and methods

Results

Conclusions

Clinical relevance

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Objectives

Materials and methods

Results

Conclusions

Clinical relevance

Please log in to get access to this content

Other articles of this Issue 4/2013

In vivo hemostatic efficacy of polyurethane foam compared to collagen and gelatin

The repeatability of digital shade measurement—a clinical study

Biofilm formation on stainless steel and gold wires for bonded retainers in vitro and in vivo and their susceptibility to oral antimicrobials

Effectiveness of supervised implementation of an oral health care guideline in care homes; a single-blinded cluster randomized controlled trial

Radiopacity of dental restorative materials

Mapping cavitation activity around dental ultrasonic tips