Salivary cytokines as biomarkers of periodontal diseases

Periodontology 2000

Volumn 70, Issue 1, 2016, Pages 164-183

  Jaedicke, Katrin M ^a   Preshaw, Philip M ^a   Taylor, John J ^a  

^a NONE

Author keywords

[No Author keywords available]

Indexed keywords

BIOLOGICAL MARKER; CYTOKINE;

CHEMISTRY; EARLY DIAGNOSIS; GINGIVITIS; HUMAN; PERIODONTAL DISEASES; SALIVA;

BIOMARKERS; CYTOKINES; EARLY DIAGNOSIS; GINGIVAL CREVICULAR FLUID; HUMANS; PERIODONTAL DISEASES; SALIVA;

EID: 84949660659     PISSN: 09066713     EISSN: 16000757     Source Type: Journal    
DOI: 10.1111/prd.12117     Document Type: Review

References (118)

1. Aggarwal BB, Gupta SC, Kim JH. Historical perspectives on tumor necrosis factor and its superfamily: 25 years later, a golden journey. Blood 2012: 119: 651-665.
2. Al-Sabbagh M, Alladah A, Lin Y, Kryscio RJ, Thomas MV, Ebersole JL, Miller CS. Bone remodeling-associated salivary biomarker MIP-1alpha distinguishes periodontal disease from health. J Periodontal Res 2011: 47: 389-395.
3. Aleksandra Nielsen A, Nederby Nielsen J, Schmedes A, Brandslund I, Hey H. Saliva Interleukin-6 in patients with inflammatory bowel disease. Scand J Gastroenterol 2005: 40: 1444-1448.
4. Anil S, Vellappally S, Preethanath RS, Mokeem SA, AlMoharib HS, Patil S, Chalisserry EP, Al Kheraif AA. Hepatocyte growth factor levels in the saliva and gingival crevicular fluid in smokers with periodontitis. Dis Markers 2014: 2014: 146974.
5. Aurer A, Jorgic-Srdjak K, Plancak D, Stavljenic-Rukavina A, Aurer-Kozelj J. Proinflammatory factors in saliva as possible markers for periodontal disease. Coll Antropol 2005: 29: 435-439.
6. Awang RA, Lappin DF, MacPherson A, Riggio M, Robertson D, Hodge P, Ramage G, Culshaw S, Preshaw PM, Taylor J, Nile C. Clinical associations between IL-17 family cytokines and periodontitis and potential differential roles for IL-17A and IL-17E in periodontal immunity. Inflamm Res 2014: 63: 1001-1012.
7. Barksby HE, Lea SR, Preshaw PM, Taylor JJ. The expanding family of interleukin-1 cytokines and their role in destructive inflammatory disorders. Clin Exp Immunol 2007: 149: 217-225.
8. Barksby HE, Nile CJ, Jaedicke KM, Taylor JJ, Preshaw PM. Differential expression of immunoregulatory genes in monocytes in response to Porphyromonas gingivalis and Escherichia coli lipopolysaccharide. Clin Exp Immunol 2009: 156: 479-487.
9. Baud'huin M, Duplomb L, Teletchea S, Lamoureux F, Ruiz-Velasco C, Maillasson M, Redini F, Heymann MF, Heymann D. Osteoprotegerin: multiple partners for multiple functions. Cytokine Growth Factor Rev 2013: 24: 401-409.
10. Baum BJ, Yates JR 3rd, Srivastava S, Wong DT, Melvin JE. Scientific frontiers: emerging technologies for salivary diagnostics. Adv Dent Res 2011: 23: 360-368.
11. Belibasakis GN, Bostanci N. The RANKL-OPG system in clinical periodontology. J Clin Periodontol 2012: 39: 239-248.
12. Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther 2001: 69: 89-95.
13. Booth V, Young S, Cruchley A, Taichman NS, Paleolog E. Vascular endothelial growth factor in human periodontal disease. J Periodontal Res 1998: 33: 491-499.
14. Brentano F, Schorr O, Ospelt C, Stanczyk J, Gay RE, Gay S, Kyburz D. Pre-B cell colony-enhancing factor/visfatin, a new marker of inflammation in rheumatoid arthritis with proinflammatory and matrix-degrading activities. Arthritis Rheum 2007: 56: 2829-2839.
15. Browne RW, Kantarci A, LaMonte MJ, Andrews CA, Hovey KM, Falkner KL, Cekici A, Stephens D, Genco RJ, Scannapieco FA, Van Dyke TE, Wactawski-Wende J. Performance of multiplex cytokine assays in serum and saliva among community-dwelling postmenopausal women. PLoS One 2013: 8: e59498.
16. Buduneli N, Biyikoglu B, Sherrabeh S, Lappin DF. Saliva concentrations of RANKL and osteoprotegerin in smoker versus non-smoker chronic periodontitis patients. J Clin Periodontol 2008: 35: 846-852.
17. 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.
18. Buduneli N, Ozcaka O, Nalbantsoy A. Interleukin-33 levels in gingival crevicular fluid, saliva, or plasma do not differentiate chronic periodontitis. J Periodontol 2012: 83: 362-368.
19. Chan HH, Rahim ZH, Jessie K, Hashim OH, Taiyeb-Ali TB. Salivary proteins associated with periodontitis in patients with type 2 diabetes mellitus. Int J Mol Sci 2012: 13: 4642-4654.
20. Charon JA, Luger TA, Mergenhagen SE, Oppenheim JJ. Increased thymocyte-activating factor in human gingival fluid during gingival inflammation. Infect Immun 1982: 38: 1190-1195.
21. Christodoulides N, Floriano PN, Miller CS, Ebersole JL, Mohanty S, Dharshan P, Griffin M, Lennart A, Ballard KL, King CP Jr, Langub MC, Kryscio RJ, Thomas MV, McDevitt JT. Lab-on-a-chip methods for point-of-care measurements of salivary biomarkers of periodontitis. Ann N Y Acad Sci 2007: 1098: 411-428.
22. Conde J, Scotece M, Gomez R, Lopez V, Gomez-Reino JJ, Gualillo O. Adipokines and osteoarthritis: novel molecules involved in the pathogenesis and progression of disease. Arthritis 2011: 2011: 203901.
23. Costa PP, Trevisan GL, Macedo GO, Palioto DB, Souza SL, Grisi MF, Novaes AB Jr, Taba M Jr. Salivary interleukin-6, matrix metalloproteinase-8, and osteoprotegerin in patients with periodontitis and diabetes. J Periodontol 2010: 81: 384-391.
24. Denny P, Hagen FK, Hardt M, Liao L, Yan W, Arellanno M, Bassilian S, Bedi GS, Boontheung P, Cociorva D, Delahunty CM, Denny T, Dunsmore J, Faull KF, Gilligan J, Gonzalez-Begne M, Halgand F, Hall SC, Han X, Henson B, Hewel J, Hu S, Jeffrey S, Jiang J, Loo JA, Ogorzalek Loo RR, Malamud D, Melvin JE, Miroshnychenko O, Navazesh M, Niles R, Park SK, Prakobphol A, Ramachandran P, Richert M, Robinson S, Sondej M, Souda P, Sullivan MA, Takashima J, Than S, Wang J, Whitelegge JP, Witkowska HE, Wolinsky L, Xie Y, Xu T, Yu W, Ytterberg J, Wong DT, Yates JR, 3rd, Fisher SJ. The proteomes of human parotid and submandibular/sublingual gland salivas collected as the ductal secretions. J Proteome Res 2008: 7: 1994-2006.
25. Deschner J, Eick S, Damanaki A, Nokhbehsaim M. The role of adipokines in periodontal infection and healing. Mol Oral Microbiol 2014: 29: 258-269.
26. Dinarello CA. Historical insights into cytokines. Eur J Immunol 2007: 37 (Suppl 1): S34-S45.
27. Dinarello CA. A clinical perspective of IL-1beta as the gatekeeper of inflammation. Eur J Immunol 2011: 41: 1203-1217.
28. Dunsmore SE, Rubin JS, Kovacs SO, Chedid M, Parks WC, Welgus HG. Mechanisms of hepatocyte growth factor stimulation of keratinocyte metalloproteinase production. J Biol Chem 1996: 271: 24576-24582.
29. Ebersole JL, Schuster JL, Stevens J, Dawson D 3rd, Kryscio RJ, Lin Y, Thomas MV, Miller CS. Patterns of salivary analytes provide diagnostic capacity for distinguishing chronic adult periodontitis from health. J Clin Immunol 2013: 33: 271-279.
30. Editorial. Matters of significance. Nat Methods 2013: 10: 805.
31. Fine DH, Markowitz K, Furgang D, Fairlie K, Ferrandiz J, Nasri C, McKiernan M, Donnelly R, Gunsolley J. Macrophage inflammatory protein-1alpha: a salivary biomarker of bone loss in a longitudinal cohort study of children at risk for aggressive periodontal disease? J Periodontol 2009: 80: 106-113.
32. Ford PJ, Gamonal J, Seymour GJ. Immunological differences and similarities between chronic periodontitis and aggressive periodontitis. Periodontol 2000 2010: 53: 111-123.
33. Frodge BD, Ebersole JL, Kryscio RJ, Thomas MV, Miller CS. Bone remodeling biomarkers of periodontal disease in saliva. J Periodontol 2008: 79: 1913-1919.
34. Gaffen SL, Hajishengallis G. A new inflammatory cytokine on the block: re-thinking periodontal disease and the Th1/Th2 paradigm in the context of Th17 cells and IL-17. J Dent Res 2008: 87: 817-828.
35. Gaffen SL, Jain R, Garg AV, Cua DJ. The IL-23-IL-17 immune axis: from mechanisms to therapeutic testing. Nat Rev Immunol 2014: 14: 585-600.
36. Garlanda C, Dinarello CA, Mantovani A. The interleukin-1 family: back to the future. Immunity 2013: 39: 1003-1018.
37. Giannobile WV, Al-Shammari KF, Sarment DP. Matrix molecules and growth factors as indicators of periodontal disease activity. Periodontol 2000 2003: 31: 125-134.
38. Goodson JM. Gingival crevice fluid flow. Periodontol 2000 2003: 31: 43-54.
39. Guerrini MM, Takayanagi H. The immune system, bone and RANKL. Arch Biochem Biophys 2014: 561: 118-123.
40. Gupta M, Chaturvedi R, Jain A. Role of monocyte chemoattractant protein-1 (MCP-1) as an immune-diagnostic biomarker in the pathogenesis of chronic periodontal disease. Cytokine 2013: 61: 892-897.
41. Gursoy UK, Kononen E, Uitto VJ, Pussinen PJ, Hyvarinen K, Suominen-Taipale L, Knuuttila M. Salivary interleukin-1beta concentration and the presence of multiple pathogens in periodontitis. J Clin Periodontol 2009: 36: 922-927.
42. Hefti AF, Preshaw PM. Examiner alignment and assessment in clinical periodontal research. Periodontol 2000 2012: 59: 41-60.
43. Hernandez-Molina G, Michel-Peregrina M, Hernandez-Ramirez DF, Sanchez-Guerrero J, Llorente L. Chemokine saliva levels in patients with primary Sjogren's syndrome, associated Sjogren's syndrome, pre-clinical Sjogren's syndrome and systemic autoimmune diseases. Rheumatology 2011: 50: 1288-1292.
44. Honig J, Rordorf-Adam C, Siegmund C, Wiedemann W, Erard F. Increased interleukin-1 beta (IL-1 beta) concentration in gingival tissue from periodontitis patients. J Periodontal Res 1989: 24: 362-367.
45. Hu S, Wang J, Meijer J, Ieong S, Xie Y, Yu T, Zhou H, Henry S, Vissink A, Pijpe J, Kallenberg C, Elashoff D, Loo JA, Wong DT. Salivary proteomic and genomic biomarkers for primary Sjogren's syndrome. Arthritis Rheum 2007: 56: 3588-3600.
46. Hu S, Yu T, Xie Y, Yang Y, Li Y, Zhou X, Tsung S, Loo RR, Loo JR, Wong DT. Discovery of oral fluid biomarkers for human oral cancer by mass spectrometry. Cancer Genomics Proteomics 2007: 4: 55-64.
47. Jaedicke KM, Taylor JJ, Preshaw PM. Validation and quality control of ELISAs for the use with human saliva samples. J Immunol Methods 2012: 377: 62-65.
48. Jones SA, Scheller J, Rose-John S. Therapeutic strategies for the clinical blockade of IL-6/gp130 signaling. J Clin Invest 2011: 121: 3375-3383.
49. Kakimoto K, Machigashira M, Ohnishi T, Kajihara T, Semba I, Setoguchi T, Tamura M, Izumi Y, Daikuhara Y. Hepatocyte growth factor in gingival crevicular fluid and the distribution of hepatocyte growth factor-activator in gingival tissue from adult periodontitis. Arch Oral Biol 2002: 47: 655-663.
50. Kaushik R, Yeltiwar RK, Pushpanshu K. Salivary interleukin-1beta levels in patients with chronic periodontitis before and after periodontal phase I therapy and healthy controls: a case-control study. J Periodontol 2011: 82: 1353-1359.
51. Kibayashi M, Tanaka M, Nishida N, Kuboniwa M, Kataoka K, Nagata H, Nakayama K, Morimoto K, Shizukuishi S. Longitudinal study of the association between smoking as a periodontitis risk and salivary biomarkers related to periodontitis. J Periodontol 2007: 78: 859-867.
52. Kinane DF, Preshaw PM, Loos BG. Host-response: understanding the cellular and molecular mechanisms of host-microbial interactions-consensus of the Seventh European Workshop on Periodontology. J Clin Periodontol 2011: 38 (Suppl 11): 44-48.
53. Kinney JS, Ramseier CA, Giannobile WV. Oral fluid-based biomarkers of alveolar bone loss in periodontitis. Ann N Y Acad Sci 2007: 1098: 230-251.
54. Kinney JS, Morelli T, Braun T, Ramseier CA, Herr AE, Sugai JV, Shelburne CE, Rayburn LA, Singh AK, Giannobile WV. Saliva/pathogen biomarker signatures and periodontal disease progression. J Dent Res 2011: 90: 752-758.
55. Kojima T, Andersen E, Sanchez JC, Wilkins MR, Hochstrasser DF, Pralong WF, Cimasoni G. Human gingival crevicular fluid contains MRP8 (S100A8) and MRP14 (S100A9), two calcium-binding proteins of the S100 family. J Dent Res 2000: 79: 740-747.
56. Kornman KS, Page RC, Tonetti MS. The host response to the microbial challenge in periodontitis: assembling the players. Periodontol 2000 1997: 14: 33-53.
57. Lassere MN. The Biomarker-Surrogacy Evaluation Schema: a review of the biomarker-surrogate literature and a proposal for a criterion-based, quantitative, multidimensional hierarchical levels of evidence schema for evaluating the status of biomarkers as surrogate endpoints. Stat Methods Med Res 2008: 17: 303-340.
58. Lehr S, Hartwig S, Sell H. Adipokines: a treasure trove for the discovery of biomarkers for metabolic disorders. Proteomics Clin Appl 2012: 6: 91-101.
59. Luzina IG, Keegan AD, Heller NM, Rook GA, Shea-Donohue T, Atamas SP. Regulation of inflammation by interleukin-4: a review of "alternatives". J Leukoc Biol 2012: 92: 753-764.
60. MacFarlane LA, Todd DJ. Kinase inhibitors: the next generation of therapies in the treatment of rheumatoid arthritis. Int J Rheum Dis 2014: 17: 359-368.
61. Matsumoto K, Nakamura T. Hepatocyte growth factor (HGF) as a tissue organizer for organogenesis and regeneration. Biochem Biophys Res Commun 1997: 239: 639-644.
62. Mergenhagen SE. Thymocyte activating factor(s) in human gingival fluids. J Dent Res 1984: 63: 461-464.
63. Miller CS, King CP Jr, Langub MC, Kryscio RJ, Thomas MV. Salivary biomarkers of existing periodontal disease: a cross-sectional study. J Am Dent Assoc 2006: 137: 322-329.
64. Mirrielees J, Crofford LJ, Lin Y, Kryscio RJ, Dawson DR 3rd, Ebersole JL, Miller CS. Rheumatoid arthritis and salivary biomarkers of periodontal disease. J Clin Periodontol 2010: 37: 1068-1074.
65. Molnarfi N, Benkhoucha M, Funakoshi H, Nakamura T, Lalive PH. Hepatocyte growth factor: a regulator of inflammation and autoimmunity. Autoimmun Rev 2015: 14: 293-303.
66. Moschen AR, Kaser A, Enrich B, Mosheimer B, Theurl M, Niederegger H, Tilg H. Visfatin, an adipocytokine with proinflammatory and immunomodulating properties. J Immunol 2007: 178: 1748-1758.
67. Ng PY, Donley M, Hausmann E, Hutson AD, Rossomando EF, Scannapieco FA. Candidate salivary biomarkers associated with alveolar bone loss: cross-sectional and in vitro studies. FEMS Immunol Med Microbiol 2007: 49: 252-260.
68. Nishida N, Yamamoto Y, Tanaka M, Maeda K, Kataoka K, Nakayama K, Morimoto K, Shizukuishi S. Association between passive smoking and salivary markers related to periodontitis. J Clin Periodontol 2006: 33: 717-723.
69. Ogawa H, Damrongrungruang T, Hori S, Nouno K, Minagawa K, Sato M, Miyazaki H. Effect of periodontal treatment on adipokines in type 2 diabetes. World J Diabetes 2014: 5: 924-931.
70. Ohnishi T, Daikuhara Y. Hepatocyte growth factor/scatter factor in development, inflammation and carcinogenesis: its expression and role in oral tissues. Arch Oral Biol 2003: 48: 797-804.
71. Ohshima M, Noguchi Y, Ito M, Maeno M, Otsuka K. Hepatocyte growth factor secreted by periodontal ligament and gingival fibroblasts is a major chemoattractant for gingival epithelial cells. J Periodontal Res 2001: 36: 377-383.
72. Olsen CH. Review of the use of statistics in infection and immunity. Infect Immun 2003: 71: 6689-6692.
73. Ouyang W, Rutz S, Crellin NK, Valdez PA, Hymowitz SG. Regulation and functions of the IL-10 family of cytokines in inflammation and disease. Annu Rev Immunol 2011: 29: 71-109.
74. Ozcaka O, Nalbantsoy A, Buduneli N. Interleukin-17 and interleukin-18 levels in saliva and plasma of patients with chronic periodontitis. J Periodontal Res 2011: 46: 592-598.
75. Ozcan E, Saygun NI, Serdar MA, Kurt N. Evaluation of the salivary levels of visfatin, chemerin, and progranulin in periodontal inflammation. Clin Oral Invest 2014: 19: 921-928.
76. Pihlstrom BL, Michalowicz BS, Johnson NW. Periodontal diseases. Lancet 2005: 366: 1809-1820.
77. Prakasam S, Srinivasan M. Evaluation of salivary biomarker profiles following non-surgical management of chronic periodontitis. Oral Dis 2014: 20: 171-177.
78. Preshaw PM. Definitions of periodontal disease in research. J Clin Periodontol 2009: 36: 1-2.
79. 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.
80. Ramseier CA, Kinney JS, Herr AE, Braun T, Sugai JV, Shelburne CA, Rayburn LA, Tran HM, Singh AK, Giannobile WV. Identification of pathogen and host-response markers correlated with periodontal disease. J Periodontol 2009: 80: 436-446.
81. Rathnayake N, Akerman S, Klinge B, Lundegren N, Jansson H, Tryselius Y, Sorsa T, Gustafsson A. Salivary biomarkers for detection of systemic diseases. PLoS One 2013: 8: e61356.
82. Rathnayake N, Akerman S, Klinge B, Lundegren N, Jansson H, Tryselius Y, Sorsa T, Gustafsson A. Salivary biomarkers of oral health: a cross-sectional study. J Clin Periodontol 2013: 40: 140-147.
83. Razali NMWY. Power comparisons of Shapiro-Wilk, Kolmogorov-Smirnov, Lilliefors and Anderson-Darling tests. J Stat Model Analytics 2011: 2: 21-33.
84. Rincon M. Interleukin-6: from an inflammatory marker to a target for inflammatory diseases. Trends Immunol 2012: 33: 571-577.
85. Rudrakshi C, Srinivas N, Mehta DS. A comparative evaluation of hepatocyte growth factor levels in gingival crevicular fluid and saliva and its correlation with clinical parameters in patients with and without chronic periodontitis: a clinico-biochemical study. J Indian Soc Periodontol 2011: 15: 147-151.
86. Salazar MG, Jehmlich N, Murr A, Dhople VM, Holtfreter B, Hammer E, Volker U, Kocher T. Identification of periodontitis associated changes in the proteome of whole human saliva by mass spectrometric analysis. J Clin Periodontol 2013: 40: 825-832.
87. Salminen A, Gursoy UK, Paju S, Hyvarinen K, Mantyla P, Buhlin K, Kononen E, Nieminen MS, Sorsa T, Sinisalo J, Pussinen PJ. Salivary biomarkers of bacterial burden, inflammatory response, and tissue destruction in periodontitis. J Clin Periodontol 2014: 41: 442-450.
88. Saxena A, Khosraviani S, Noel S, Mohan D, Donner T, Hamad AR. Interleukin-10 paradox: a potent immunoregulatory cytokine that has been difficult to harness for immunotherapy. Cytokine 2014: 74: 27-34.
89. Scannapieco FA, Ng P, Hovey K, Hausmann E, Hutson A, Wactawski-Wende J. Salivary biomarkers associated with alveolar bone loss. Ann N Y Acad Sci 2007: 1098: 496-497.
90. Schulz BL, Cooper-White J, Punyadeera CK. Saliva proteome research: current status and future outlook. Crit Rev Biotechnol 2013: 33: 246-259.
91. Sedger LM, McDermott MF. TNF and TNF-receptors: from mediators of cell death and inflammation to therapeutic giants - past, present and future. Cytokine Growth Factor Rev 2014: 25: 453-472.
92. Sexton WM, Lin Y, Kryscio RJ, Dawson DR 3rd, Ebersole JL, Miller CS. Salivary biomarkers of periodontal disease in response to treatment. J Clin Periodontol 2011: 38: 434-441.
93. Seymour GJ, Taylor JJ. Shouts and whispers: an introduction to immunoregulation in periodontal disease. Periodontol 2000 2004: 35: 9-13.
94. Silva TA, Garlet GP, Fukada SY, Silva JS, Cunha FQ. Chemokines in oral inflammatory diseases: apical periodontitis and periodontal disease. J Dent Res 2007: 86: 306-319.
95. Singh JA, Christensen R, Wells GA, Suarez-Almazor ME, Buchbinder R, Lopez-Olivo MA, Ghogomu ET, Tugwell P. A network meta-analysis of randomized controlled trials of biologics for rheumatoid arthritis: a Cochrane overview. Can Med Assoc J 2009: 181: 787-796.
96. Singh P, Gupta ND, Bey A, Khan S. Salivary TNF-alpha: a potential marker of periodontal destruction. J Indian Soc Periodontol 2014: 18: 306-310.
97. Slots J. Periodontology: past, present, perspectives. Periodontol 2000 2013: 62: 7-19.
98. Sugiyama A, Arakaki R, Ohnishi T, Arakaki N, Daikuhara Y, Takada H. Lipoteichoic acid and interleukin 1 stimulate synergistically production of hepatocyte growth factor (scatter factor) in human gingival fibroblasts in culture. Infect Immun 1996: 64: 1426-1431.
99. Tabari ZA, Azadmehr A, Tabrizi MA, Hamissi J, Ghaedi FB. Salivary soluble receptor activator of nuclear factor kappa B ligand/osteoprotegerin ratio in periodontal disease and health. J Periodontal Implant Sci 2013: 43: 227-232.
100. Tabari ZA, Azadmehr A, Nohekhan A, Naddafpour N, Ghaedi FB. Salivary visfatin concentrations in patients with chronic periodontitis. J Periodontol 2014: 85: 1081-1085.
101. Taylor JJ, Preshaw PM, Lalla E. A review of the evidence for pathogenic mechanisms that may link periodontitis and diabetes. J Clin Periodontol 2013: 40 (Suppl 14): S113-S134.
102. Taylor JJ. Protein biomarkers of periodontitis in saliva. ISRN Inflamm 2014: 2014: 593151.
103. Teles RP, Likhari V, Socransky SS, Haffajee AD. Salivary cytokine levels in subjects with chronic periodontitis and in periodontally healthy individuals: a cross-sectional study. J Periodontal Res 2009: 44: 411-417.
104. Tobon-Arroyave SI, Jaramillo-Gonzalez PE, Isaza-Guzman DM. Correlation between salivary IL-1beta levels and periodontal clinical status. Arch Oral Biol 2008: 53: 346-352.
105. Tobon-Arroyave SI, Isaza-Guzman DM, Restrepo-Cadavid EM, Zapata-Molina SM, Martinez-Pabon MC. Association of salivary levels of the bone remodelling regulators sRANKL and OPG with periodontal clinical status. J Clin Periodontol 2012: 39: 1132-1140.
106. Tomar SL, Asma S. Smoking-attributable periodontitis in the United States: findings from NHANES III. National Health and Nutrition Examination Survey. J Periodontol 2000: 71: 743-751.
107. 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: 2563-2582.
108. Urdea MS, Neuwald PD, Greenberg BL, Glick M, Galloway J, Williams D, Wong DT. Saliva, diagnostics, and dentistry. Adv Dent Res 2011: 23: 353-359.
109. van de Veerdonk FL, Netea MG. New insights in the immunobiology of IL-1 family members. Front Immunol 2013: 4: 167.
110. van Tuyl LH, Voskuyl AE, Boers M, Geusens P, Landewe RB, Dijkmans BA, Lems WF. Baseline RANKL:OPG ratio and markers of bone and cartilage degradation predict annual radiological progression over 11 years in rheumatoid arthritis. Ann Rheum Dis 2010: 69: 1623-1628.
111. Vastardis S, Leigh JE, Wozniak K, Yukna R, Fidel PL Jr. Influence of periodontal disease on Th1/Th2-type cytokines in saliva of HIV-positive individuals. Oral Microbiol Immunol 2003: 18: 88-91.
112. Warnock DG, Peck CC. A roadmap for biomarker qualification. Nat Biotechnol 2010: 28: 444-445.
113. Wilczynska-Borawska M, Borawski J, Kovalchuk O, Chyczewski L, Stokowska W. Hepatocyte growth factor in saliva is a potential marker of symptomatic periodontal disease. J Oral Sci 2006: 48: 47-50.
114. Wilczynska-Borawska M, Borawski J, Baginska J, Malyszko J, Mysliwiec M. Hepatocyte growth factor in saliva of patients with renal failure and periodontal disease. Ren Fail 2012: 34: 942-951.
115. Wong DT. Salivary diagnostics powered by nanotechnologies, proteomics and genomics. J Am Dent Assoc 2006: 137: 313-321.
116. Wu Y, Shu R, Luo LJ, Ge LH, Xie YF. Initial comparison of proteomic profiles of whole unstimulated saliva obtained from generalized aggressive periodontitis patients and healthy control subjects. J Periodontal Res 2009: 44: 636-644.
117. Yoon AJ, Cheng B, Philipone E, Turner R, Lamster IB. Inflammatory biomarkers in saliva: assessing the strength of association of diabetes mellitus and periodontal status with the oral inflammatory burden. J Clin Periodontol 2012: 39: 434-440.
118. Zabel BA, Kwitniewski M, Banas M, Zabieglo K, Murzyn K, Cichy J. Chemerin regulation and role in host defense. Am J Clin Exp Immunol 2014: 3: 1-19.