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 Table of Contents  
REVIEW ARTICLE
Year : 2019  |  Volume : 11  |  Issue : 6  |  Page : 135-139  

Gingival crevicular fluid: An overview


Department of Periodontics, Madha Dental College and Hospital, Chennai, Tamil Nadu, India

Date of Web Publication28-May-2019

Correspondence Address:
Dr. Krishnan Chandragiri Subbarao
Department of Periodontics, Madha Dental College and Hospital, Chennai 600069, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JPBS.JPBS_56_19

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   Abstract 

Gingival crevicular fluid is an inflammatory exudate derived from the periodontal tissues. It is composed of serum and locally generated materials such as tissue breakdown products, inflammatory mediators, and antibodies directed against dental plaque bacteria. It plays a special part in maintaining the structure of junctional epithelium and the antimicrobial defense of periodontium. Some of the suspected periodontal pathogens such as Porphyromonas gingivalis and Treponema denticola produce broad-spectrum neutral proteinases as part of their virulence arsenal. These proteinases may be detected in plaque and gingival crevicular fluid samples of patients with periodontitis. The potential diagnostic importance of gingival fluid was recognized more than six decades ago. The fluid component of gingival crevicular fluid is derived primarily from microvascular (postcapillary venule) leakage. There are number of distinct advantages and challenges of using gingival crevicular fluid as a diagnostic test for periodontal disease.

Keywords: Exudate, leukocytes, periodontium


How to cite this article:
Subbarao KC, Nattuthurai GS, Sundararajan SK, Sujith I, Joseph J, Syedshah YP. Gingival crevicular fluid: An overview. J Pharm Bioall Sci 2019;11, Suppl S2:135-9

How to cite this URL:
Subbarao KC, Nattuthurai GS, Sundararajan SK, Sujith I, Joseph J, Syedshah YP. Gingival crevicular fluid: An overview. J Pharm Bioall Sci [serial online] 2019 [cited 2019 Jun 18];11, Suppl S2:135-9. Available from: http://www.jpbsonline.org/text.asp?2019/11/6/135/258882




   Introduction Top


Gingival crevicular fluid (GCF) is an inflammatory exudate derived from the periodontal tissues. It is composed of serum and locally generated materials such as tissue breakdown products, inflammatory mediators, and antibodies directed against dental plaque bacteria. Its constituents are derived from a number of sources, including serum, the connective tissue, and epithelium through which GCF passes on its way to the crevice.[1] GCF plays a special part in maintaining the structure of junctional epithelium and the antimicrobial defense of periodontium.

Various investigators[2] have confirmed that GCF is a complex mixture of substances derived from serum, leukocytes, and structural cells of the periodontium and oral bacteria.


   Junctional Epitheliuminthe Antimicrobial Defense Top


The junctional epithelium is firmly attached to the tooth and thus forms an epithelial barrier against the plaque bacteria and allows the access of GCF, inflammatory cells, and components of the immunological host defense to the gingival margin. It also exhibits rapid turnover, which contributes to the host–parasite equilibrium and rapid repair of damaged tissues.

GCF is an exudate of varying composition found in the sulcus/periodontal pocket between the tooth and marginal gingiva. It contains components of serum, inflammatory cells, connective tissue, epithelium, and microbial flora inhabiting the gingival margin or the sulcus/pocket. In the healthy sulcus, the amount of GCF is very less.

During inflammation, the GCF flow increases and its composition starts to resemble that of an inflammatory exudate. The increased GCF flow contributes to host defense by flushing bacterial colonies and their metabolites away from the sulcus. The main route for GCF diffusion is through the basement membrane and then through the junctional epithelium into the sulcus.


   Mechanismof Gingival Crevicular Fluid Production Top


Molecular sieving

Two events occurring in the inflammatory process are responsible for molecular sieving:

  1. a rise of hydrostatic pressure within the microcirculation and


  2. unlocking of endothelial cell junctions [Figure 1].
Figure 1: Mechanism of gingival crevicular fluid production

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Egelberg[3] obtained an increased permeability of the blood vessels of healthy gingiva by the use of three different methods, such as topical application of histamine, gentle massage of gingiva by a ball-ended amalgam plugger, and scrapping of the gingival crevice by a blunt dental explorer.

Gingival crevicular fluid flow

GCF flow is the process of fluid moving into and out of the gingival crevice or pocket. It is a small stream, usually only a few microliters per hour. Fluid flow is a rate measure. It is the volume that crosses a defined boundary over a given time, mathematically symbolized as dV/dt, the first derivative of volume with respect to time.

Significance of gingival crevicular fluid

  1. To assess the severity of gingival diseases, the effectiveness of periodontal therapy and oral hygiene, the healing following gingival surgery, and the effectiveness of oral hygiene.


  2. To evaluate the rate of local destruction, to assess the permeability of junctional and sulcular epithelium, and to assess the relationship between periodontal and systemic diseases.


Factors stimulating gingival crevicular fluid flow

  1. Gingival inflammation, mastication of coarse food, pocket depth, intracrevicular scraping, scaling, and histamine topical application.


  2. Enzymes and sex hormones: Female sex hormones increase the gingival fluid flow because they enhance vascular permeability.


  3. Circadian periodicity: There is gradual increase in gingival fluid amount from 6 am to 10 pm and a decrease afterward.


  4. Post-periodontal surgery, restorative procedure, strip placement, mobility, increased body temperature, and salivary contamination.


  5. Ovulation, hormonal contraceptives, and smoking.


[TAG:2]Methods of Collection[/TAG:2]

Absorbing paper strips

Filter paper strips were used to collect GCF by inserting the strips into the crevice (apical direction) until mild resistance was detected or by inserting the strips at or over the entrance of the pocket to pick up the seeping fluid.

The fluid volume on the strips was quantified by a number of ways:

  1. Originally, strips were stained with a protein disclosing dye such as ninhydrin at concentration varying between 0.2% and 2%. The stained area can be measured by using a magnifying device such as a graded microscope.


  2. The strips were weighed before collection within a scaled microcentrifugation plastic tube and the weighing was repeated immediately after collection in the same microtubule.


  3. An electronic method has been devised for measuring the fluid collected on a blotter (PerioPaper) using an electronic transducer (Periotron). This electronic device measures the changes in capacitance across the wetted strip. This change is converted into a digital readout that can be correlated to the volume of GCF.


Preweighed twisted threads

The threads were placed in the gingival crevice around the tooth, and the amount of fluid collected was estimated by weighing the sample threads.[4]

Micropipettes

The use of micropipettes permits the absorption of fluid by capillarity. Capillary tubes of standardized length and diameter were placed in the pocket and their content was later centrifuged and analyzed. The capillary tubes may contaminate native GCF by the influx of serum following disruption of the gingival vasculature.

Crevicular washings

The appliance designed by Oppenheim permits collection of gingival fluid without disturbing the integrity of the marginal gingiva and this is a modification of that described by Takamori[5] and the acrylic splint. It consists of a hard acrylic plate covering the maxilla with soft borders and a groove along the gingival margin, which is connected to four plastic cubes. Gingival washings are obtained by rinsing the sulcular area for a fixed period from one side to another through the palatine and buccal channels with 4–6mL of solution using a peristaltic pump.

[TAG:2]Composition of Gingival Crevicular Fluid[/TAG:2]

Cellular elements

Epithelial cells

Fluid originating from areas with more severe gingivitis contained a much higher proportion of cells typical to the deepest epithelial layer.

Leukocytes

It has been established that 47% of somatic cells obtained from the gingival sulcus were leukocytes, whereas the presence of inflammatory cells in the gingival crevice showed 98% of polymorphonuclear cells. The absolute number of cells increased proportionately with the intensity of inflammation, whereas the differential count was 95–97% neutrophils, 1–2% lymphocytes, and 2–3% mononuclear cells.

Bacteria

Bacteria cultured from GCF were similar to those found in the adjacent dental plaque electrolyte.

Electrolytes

Na:K

Na:K ratio in GCF is 3:9 as opposed to its ratio of 28:1, which confirms that the fluid passes through damaged tissue due to accumulation of intracellular potassium from disrupted cells.[6]

Fluoride, calcium, iodine, and phosphorus

Minerals.

Organic compounds

Carbohydrates

Glucose hexosamine and hexuronic acid are two of the compounds found in gingival fluid.

Proteins

The total protein content of gingival fluid is much less than that of serum.

Immunoglobulins

The total immunoglobulin in GCF does not correlate with disease severity or progressions and indeed may be lower at progressive sites.

Complement

Complement proteins are present in GCF from sites with inflammation and the split fragments C3 and factor B have been detected during experimental gingivitis.

Cytokines

Interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-α) are produced by activated macrophages and other cells. IL-1α and IL-1β are present in inflamed gingiva.

Metabolic and bacterial products

Metabolic products, amino acids and harmones: Metabolic products such as lactic acid found in gcf. Amino acid such as hydroxyproline is found in gcf, and harmone such a sprostoglandin is found in gcf.


   Enzymes Top


Proteolytic and hydrolytic enzymes of inflammatory cell origin

Inflammatory process leads to the release of polymorphonuclear neutrophils or leukocytes (PMN), macrophages, lymphocytes, and mast cells.The lysosomes of these inflammatory cells contain destructive enzymes that degrade the bacterial and metabolic by products during the process of phagocytosis. These enzymes are, however, capable of degrading gingival tissue components if released.


   Collagenases and Related Metalloproteinase Top


Collagenases are a part of matrix metalloproteinase family that degrades collagen. They are synthesized by macrophages, neutrophils, and fibroblasts and keratinocytes are secreted by these cells as latent enzymes when stimulated by some bacterial products and cytokines. Total enzyme activity levels were significantly higher and enzyme inhibitor levels were lower at diseased sites compared with healthy or treated sites.[7]

Cysteine proteinases

Cathepsins B, L, and H are a family of cellular cysteine proteinases, which can degrade extracellular components including collagen. They act at acidic pH and are particularly active during bone resorption. They are also produced principally by fibroblasts, macrophages, and osteoclasts.[8] Levels of cathepsins B and C were significantly reduced following periodontal treatment.[9]

Aspartate proteinases

Cathepsin D is found in gingival tissue, and GCF levels have been shown to correlate significantly with increasing gingival inflammation, probing depth, probing attachment level, and bone loss.[10]

Serine proteinases

Elastase

Active elastase can only occasionally be detected in gingival tissue and is usually seen adjacent to junctional epithelium where PMNs are migrating into the crevice or in granulation tissue at the advancing front of the lesion.[11]

Tryptase

Tryptase activity is present in large amounts in gingival tissue and in small amounts in GCF and has been localized to gingival mast cells.[12] Tryptase stimulates the release of collagenase from gingival fibroblasts and in inflamed gingival tissues.

[TAG:2]Dipeptidyl peptidase[/TAG:2]

Dipeptidyl peptidase II (DPP II), which is active at acidic pH, and DPP IV, which is active at alkaline pH, are present in gingival tissue and GCF.

Myeloperoxidase, lysosome, and lactoferrin

Myeloperoxidase is a potent bacterial enzyme produced by PMNs, which are higher at periodontal disease sites than healthy sites, whereas lysosomes are found in body secretions notably tears and saliva and in GCF. Lactoferrin is an antibacterial agent produced by inflammatory cells, which are found in GCF.

[TAG:2]Aspartate Aminotransferase and Lactate Dehydrogenase[/TAG:2]

Aspartate aminotransferase is confined to the cell cytoplasm that is released by dead or dying cells, whereas lactate dehydrogenase is present in the cytoplasm of erythrocytes, thrombocytes, and leukocytes.


   Markers of Connective Tissue Degradation Top


The markers of connective tissue degradation present in gcf are namely types I, III, and IV collagen, proteoglycans, hyaluronan, fibronectin, laminin, and bone-specific proteins.

[TAG:2]Drugs in the Sulcular Fluid[/TAG:2]

Metronidazole and tetracycline can eliminate tissue bacteria, and in conjunction with scaling and root planning, they suppress actinomycetemcomitans levels. Tetracycline in low doses inhibits the activity of collagenase and other collagenolytic enzymes.

[TAG:2]Gingival Crevicular Fluid and Implants[/TAG:2]

The levels of neutral proteases were higher at moderately to severely inflamed implant sites compared to mildly inflamed sites. The levels of neutrophil elastase, myeloperoxidase, and β-glucuronidase were significantly higher around sailing implants compared to successful implants.

The levels of IL-1β were approximately three times higher than those of the healthy sites in GCF around implants. Significantly low activity of elastase and collagenase was detected in osseointegrated implants than in adult periodontitis.


   Summaryand Conclusion Top


The studies of GCF chemistry have suggested the importance of an exuberant PMN response to subgingival plaque in the active phases of periodontal destructions. Furthermore, the accumulated data regarding the functional status of PMN at sites of infection and inflammation suggest that the tissue destruction associated with an influx of PMN is a result of PMN hyperactivity. Further studies should focus on defining the equilibrium and identifying shifts in the equilibrium that occur with different periodontal diseases and the related changes in GCF chemistry.

The search for markers of periodontal disease activity and progression has accelerated over the last decade and research is being aimed at establishing a more objective and quantitative methodology, capable of rapid diagnosis prior to the appearance of clinical signs of destructive disease. GCF has emerged in the last decade as a new domain for improved periodontal diagnosis and therapy. However, further longitudinal and cross-sectional studies are required to unequivocally establish their credence as potential markers.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Lamster IB. Evaluation of components of gingival crevicular fluid as diagnostic tests. Ann Periodontal 1997;2:123-37.  Back to cited text no. 1
    
2.
Eley BM, Cox SW. Proteolytic and hydrolytic enzymes from putative periodontal pathogens: Characterization, molecular genetics, effects on host defenses and tissues and detection in gingival crevice fluid. Periodontol 2000 2003;31:105-24.  Back to cited text no. 2
    
3.
Egelberg J. Permeability of the dento-gingival blood vessels: I. Application of the vascular labelling method and gingival fluid measurements. J Periodontal Res 1966;1:181-91.  Back to cited text no. 3
    
4.
Weinstein E, Khurana H, Madel ID. Lactate dehydrogenase isoenzymes in gingival fluid. Arch Oral Biol 1972;13:375-6.  Back to cited text no. 4
    
5.
Takamori K. The growth stimulating factors for lactobacillus appeared in tissue fluid from gingival crevice. Bull Tokyo Med Dent Univ 1963;10:533  Back to cited text no. 5
    
6.
Krasse B, Egelberg J. The relative proportions of sodium, potassium and calcium in gingival pocket fluid. Acta Odontol Scand 1962;2:143-52.  Back to cited text no. 6
    
7.
Larivée J, Sodek J, Ferrior JM. Collagenase and collagenase inhibitor activity in crevicular fluid of patients receiving treatment for localized juvenile periodontitis. J Periodontal Res 1986;21:702-15.  Back to cited text no. 7
    
8.
Kennet CN, Cox SW, Eley BM. Comparative histochemical, biochemical and immune-cyto-chemical studies of cathepsin B in human gingiva. J Peridontal Res 1994;29:203-13.  Back to cited text no. 8
    
9.
Eley BM, Cox SW. Crevicular fluid dipeptidyl peptidase activities before and after periodontal treatment. J Dent Res 1992;71:622-32.  Back to cited text no. 9
    
10.
Ishikawa I, Cimasoni G. Possible role of lysosomal enzymes in the pathogens of periodontitis: A study of cathepsin D in human gingival fluid. Arch Oral Biol 1972;17:111-7.  Back to cited text no. 10
    
11.
Golub LM, Siegel K, Ramamurthy NS, Mandel ID. Some characteristics of collagenase activity in gingival crevicular fluid and its relationship in gingival disease in humans. J Dent Res 1976;55:1049-57.  Back to cited text no. 11
    
12.
Kennet CN, Cox SW, Eley BM. Localization of active and inactive elastase alpha 1 proteinase inhibitor and alpha-2 macroglobulin in human gingiva. J Dent Res 1995;74:667-74.  Back to cited text no. 12
    


    Figures

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    Abstract
    Markers of Conne...
    Drugs in theSulc...
    Gingival Crevicu...
    Summaryand Concl...
   Introduction
    Junctional Epith...
    Mechanismof Ging...
   Methodsof Collection
    Compositionof Gi...
   Enzymes
    Collagenases and...
   Dipeptidylpeptidase
    Aspartate Aminot...
    References
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