Jpn. J. Infect. Dis., 54, 69171, 2001

Original Article

Periodontitis and Semm lnterleukin‑6 Levels in the Elderly
Takatoshi Murata*, Hideo Miyazaki, Hidenobu Senpukul and Nobuhiro HanadaI
Departmen i ofPyleVentive Den tistyy, Faculy ofDentistTy, Niigata Un iversiO!,
Gakkocho‑dori 2152 74, Niigata 951‑851 4 andIDepartment of Oral Science, National Institute ofInfectious Diseases,

Toyama I‑23‑1, Shinjuku‑ku, Tob70 162‑8640, Japan(Received January 4, 2001. Accepted May 14, 2001)
SUMMARY: The elderly lose teeth as a result of dental caries and periodontitis caused by pathogenic oralbacteria. Periodontitis produces inflammatory cytokines due to the presence of lipopolysaccharidesfrom oralgram‑negative bacteria. Althoughthe number of circulating inflammatory cytokines is related to the severity ofthe periodontitis, it is unclear whether the concentrations also co汀elate with periodontitis in the elderly･ We

investigated the relationship between periodontitis status and the concentrations of semm interleukin‑6 (lL6) inthe serum from 276 subjects of70‑ and 80‑yearl01ds. Ofthe 276 subjects, 227 (82%) were dentate, 149 (54%)
were found to be positive for serum IL‑6, and 29 (1 3%) of the dentate subjects had severe periodontitis･ However,there were no slgnificant differences between the severity Ofperiodontitis or the number of teeth and the mean
serum IL‑6 concentrations. These results provided no evidence to support an association between circulating IL‑6and periodontitis in the elderly.

tions.

INTRODUCTION

Oral examinations: Four trainedand experienced dentists

Periodontitis is a major oral disease caused by gram‑negativebacteria in dentate people. Gram‑negative bacteria that cause

assessed the oral health of the subjects under sufrlCientperiodontitis affect systemic health, Sometimes leading tosubjects'teeth, including any decayed and misslng teeth, wassevere sepsis ( 1 ). Major clinical manifestations of sepsis havebeen caused by proinflarrmatory cytokines such as interleukin‑assessed in accordance with World Health Organization

6 (IL‑6) that are produced by lipopolysaccharide (LPS)

pointed periodontal probes (Vivadent, Schaan, Liechtenstein),

illumination provided by artificial light. The condition of(WHO) criteria (13), using dental mirrors and WHO bal1‑

derived from gram negative bacteria (2,3).Asthe concentra‑

without hurting the periodontal tissue. The periodontal condi‑

tions of seruminflammatory cytokines are related to thetions for all teeth,including bleeding upon probing,periodontal

severity and the outcome of sepsis (4,5), innammatory

probing depths, and loss of attachment in millimeters werecytokines can be used as possible predictors of disease (6‑9)･

recorded. The fわur examiners were calibrated on volunteer

Detection of the proinflammatory cytokine IL‑6 Stimulated

patients at the Universlty Hospital befわre and during theby bacterial LPS and the role of this cytokine in destroying

survey. Kappa values between each pair of examiners wereperiodontal tissue have been extensively studied both in sites

in the range ofO.8 1 to 0.63 for assesslng Periodontal condi‑of localized periodontitis (10) and in vitro (1 I , 12)I Howe.ver･tlOnS.

the relationship between periodontitis and the concentratlOnS

MeasuremerLt Of serum IL‑6: Blood samples wereof circulating inflammatory IL‑6 has not been investigatedcollected in order to determine cytokine concentrations. Clottedwith regard to the decreaslng resistance of the elderly toblood samples were centrifuged immediately at 3,000 rpm

bacteria due to aglng and accumulating bacteria in the oral

for 10 min, and the serum was stored at ‑80oC. The levels ofserum lL‑6 Were analyzed uslng COmmerCially available

cavlty･EuSA kits (Endgen, Inc., Wobum, Mass., USA) and follow‑

In this study, We assessedthe relationship between periodon‑

ing the manufacturer's instructions･ The manufacturer

titis and the semm concentrations of IL‑6 in elderly people.

reported the sensitivlty thresholds as l pg/ml f♭r IL‑6･ Tb

avoid interobserver variation, all measurements were

MATERIALS AND METHODS

performed by a slngle trained individual･ All samples wereStudy population: We chose a study sample of 276 subjects,

assayed in duplicate･Composed of 207 (1 12 males and 95 females) 70‑year‑olds

Statistical analysis: Before examinlng the study data, alland 69 (30 males and 39 females) 80lyear‑01ds. None of thecut‑offPolntS for categories of variables were determined･subjects was hospitalized or institutionalized, and each came

The number of teeth present was categorized into four groups

to血e examination center either alone or accompanied by theirbased on our knowledge or the distribution of the number offamily. They were in good general health and did not require

teeth present in subjects admitted to the study wards: edentu‑

special care fb∫ their day‑to‑day activities. Infbmed consent

lous, 1 to 9 teeth, 10 to 19 teeth, and 20 teeth or more. Thewas obtained &om all subjects prior tO the study, allowlng uSseventy of periOdontal disease was dichotomized as moderate

to ascertain their oral health statusand serum IL‑6 concentra‑

or severe based on the presence of both periodontal pockets
more than 6 mm in depth and bleeding upon probing at the*Corresponding author: Tel: +8 1 ‑25‑227‑2858, Fax: +8 1 ‑25‑227‑

same periodontal pocket in dentate subjects･ Statistical

0807, E‑mail: tmurata@dent.niigata‑u.acjp

analysts Of the data was based on the Student's ∫‑test to69

compare age and gender differences with the mean concentra‑

ing･ According to WHO criteria ( 1 3), Complex professionaltions of IL‑6. One‑factor analysis of variance (ANOVA) was

treatment is indicated fb∫ periodontitis assoclated with aused to determine the association between serum IL‑6 levels

periodontal pocket 6 mm or more in depth. However suchand the number of teeth present. Allanalyses were performed
using the statistical program STATVIEW Version 4.5 (Abacustion but may suggest an experience of past severe inflamma‑

Cbnceptus, lnc., Berkeley, Calif., USA).

tory disease or a current stable inflammatory condition.

deeper periodontal pockets do not always present inflamma‑

Accordingly, We dichotomized the severlty Of periodontal
disease as "moderate" or …severe" based on the presence ofRES UIXS

bothperiodontalpockets more than 6 mm in depthand bleeding
upon probing at the same periodontal pocket. We considered

Ofthe total sample, 227 subjects (82%) were dentate and149 (54%) were fわund to be positive f♭r semm lL‑6. Thesethe presence of such signs to be an indication of severe

dentate subjects were categorized into three groups according

periodontitis in the active phase. Ofthe 227 dentate subjects,
29 (13%) were found to have such severe stages ofperiodon'tal

to the number of teeth present. We found that serum IL‑6

disease･ There. is at least a possibilitythat temporary bacteremia
could occur lnthese subjects through subginglVal dental

concentrations did not differ slgnificantly across these threegroups (Table 1 ).

Twenty‑nine of the dentate subjects (13%) had severeplaque. We also recorded the number of teeth present, asperiodontal disease. There were no significant differences

elderly people have a tendency to accumulate inflammatory

between the mean serum lLl6 concentrations and the severity

periodontal sites when more teeth are present.

of periodontitis (Table 2). Furthermore, there were noThe release of proinnammatory cytokines, including

significant differences between the mean serum IL‑6

tumor necrosis factor, IL‑I, lLl6, and lL‑8, from activatedconcentrationsof males and those of females, or between theponocytes, macrophages, and other cells stimulated by LPS,

mean serum IL‑6 concentrationsof 70‑and 80‑year‑olds (datalS an important component of the host immune response

not shown).

(22,23)･ Septic shock has also been shown to be asso空ed

with elevated levels of these molecules (4,5). In partlCular,
IL‑6 is believed to be a good indicator of an exaggerated
Table 1. Meanconcentrations ofIL̲6 in relation to the number ofproinnammatory response, and the concentrations of circulat‑

teeth present inthe total subjects
No.of subjects(%)

Mean±SDl(pg/ml)

ing lL‑6 correlate with the severityand outcome of sepsis (24).
Many bacteria related to periodontitis are gram‑negative

Pvalue2anaerobic bacteria. The detection ofproinflarrmatory cytokine

Edentulous49 (17.8)

1‑957(20.6)

2.9±5.2

IL‑6 stimulated by bacterial LPSandthe role of this cytokinein

10‑1969 (25.0)

3.5±7.6

the destruction of periodontal tissue have been reported in20or

more

101

3. 1 ±3.9(36.6)

siteswithlocalized periodontitiS (10)andinvitro (1 1,12). In this

0.87813.8±8.3

I Less than I pg/ml was considered as 0.5 pg/ml.

context, we assessed the relationships between periodontitis

2p values were determined by ANOVA.

and the concentrations of circulating proinnammatory

cytokine IL‑6. However, we could not find any evidence tosupport a co汀elation between oral health and serum IL6

concentrations. This lack of correlation may reflect aTable 2. Mean concentrations ofIL‑6 in relation tothe severity ofdecreased ability to control infection and/or a disregulation

periodontitis in the dentate subjectsof the production of cytokines in the elderly. The circulating

Concentration of IL‑6No.ofsubjccts(%)

Meanj:SDI (pg/mI)

proinnammatory cytokine thus may not be of importance as
an indicator for an increased incidence of periodontitis withPvalue2

Peri odollti ti sModerateSevcre

increaslng age.
1 98 (87.0)29(13.0)

3.4±7.4
4.0±7.8

0.651

ACKNOWLEDGMENTS‑Lessthan I pg/ml was not detected in the EuSA and,therefore, cal‑culated as 0.5 pg/ml for convenience in the statistical analysis.

We thank Drs. Y. Ando, T. Hirotomi, and N. Takano for

2p values were determined bythe Student's I‑test.

their statistical testlng and Dr. A. Najith for his review of themanuscrlPt. This work was supported in part by a grant‑in‑aid for Scientific Research from the Ministry of Education,Culture, Sports, Science and Technology of Japan to H.M.
and N.H･ and a grant‑in‑aid from the Ministry of Health,Labour and Welfare of Japan (H‑lry0‑00 I ).

DISCUSSION
PeriOdontal diseases glVe rise to glnglVal innammation as
well as to the destruction ofperiodontal tissues, and in severecases can be accompanied by the loss ofalveolar bone with

eventual tooth loss. Both of these conditions are infectious

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