Copyright C Blackwell Munksgaard 2003

Periodontology 2000, Vol. 31, 2003, 911

Printed in Denmark. All rights reserved

PERIODONTOLOGY 2000
ISSN 0906-6713

Gingival crevice fluid

an introduction
V-J U

Studies on gingival crevice fluid (GCF) extend over

a period of about 50 years. The pioneer research of
Waerhaug in the early 1950s was focused on the anatomy of the sulcus and its transformation into a gingival pocket during the course of periodontitis (24).
In the late 1950s and early 1960s a series of groundbreaking studies by Brill et al. laid the foundation for
understanding the physiology of GCF formation and
its composition (4). The studies of Le et al. contributed to this understanding and started to explore the
use of GCF as an indicator of periodontal diseases
(17). Egelberg continued to analyze GCF and focused
his studies on the dentogingival blood vessels and
their permeability as they relate to GCF flow (6). The
GCF studies boomed in the 1970s. The rationale for
understanding dentogingival structure and physiology was created by the outstanding electron
microscopic studies of Schroeder (20) and Listgarten
(16). Presence and functions of proteins, especially
enzymes in GCF were first explored by Sueda, Bang
and Cimasoni (3, 6). It was soon understood that
enzymes released from damaged periodontal tissue
possessed an enormous potential for periodontal diagnosis. Ohlsson, Golub and Uitto discovered that
collagenase and elastase in GCF are derived primarily from human cells, most notably neutrophils, and
that their activity is correlated with gingival inflammation and gingival pocket depth (12, 18, 22).
Migration of neutrophils and their function in gingival tissue and GCF were clarified by the excellent investigations of Attstrm et al. (2). In 1974 the first
edition of the monograph The Crevicular Fluid by
Cimasoni was published (6). This comprehensive review gave a big boost to GCF studies and towards
the end of the first millenium the research on GCF
increased dramatically. Today the P M computer search of the National Library of Medicine
(USA) revealed 1656 studies on different aspects of
GCF. This volume of Periodontology 2000 reviews
some of these studies.

The review by Griffiths examines the hypothesis of

Alfano (1) which states that in health GCF represents
the transudate of gingival tissue interstitial fluid but
in the course of gingivitis and periodontitis GCF is
transformed into true inflammatory exudate. In his
review the author discusses the GCF composition
and evaluates different methods for GCF sample collection, their advantages and pitfalls (14). The flow
rate of GCF may increase about 30-fold in periodontitis compared to the healthy sulcus. However,
its resting volume also increases at the same time
with the formation of gingival pockets. Therefore,
even though the GCF flow rate when accurately
measured with an electronic device clearly reflects
the periodontal disease process, the method of fluid
collection has to be selected to provide a clear distinction between the resting volume and the flow
rate of GCF. These issues are thoroughly examined
in the review by Goodson (13).
Junctional epithelium is a unique tissue. Nowhere
else in the body does nonkeratinizing epithelium
face an inert hard tissue. This situation poses an exceptional challenge to the junctional epithelium in
the dentogingival area to protect the periodontium,
and consequently the whole body, against the several hundred bacterial species that are present in the
oral cavity. The structure and metabolism of junctional epithelium are discussed in the review by
Pllnen et al (19). The different strategies used by
junctional epithelium to overcome the microbial
challenge and reasons for the failure of the defence
systems are also described. GCF plays a special part
in maintaining the structure of junctional epithelium
and in the antimicrobial defence of periodontium.
Leukocytes, especially neutrophils, are key players in
the battle against bacteria in the sulcular region. The
article by Delima and Van Dyke deals with cells of
the GCF and the fine balance between the protective
and destructive roles of neutrophil-mediated host
defense (7). Either defective or excessive neutrophil

Uitto

function increases the risk for periodontitis dramatically.

Gingival crevice fluid (GCF) is a complex mixture
of substances derived from serum, leukocytes, structural cells of the periodontium and oral bacteria
(Fig. 1). These substances possess a great potential
for serving as indicators of periodontal disease and
healing after therapy. Some of the suspected periodontopathogens, 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
GCF samples of periodontitis patients. The properties of the oral bacterial enzymes and their value
in evaluating periodontal status are discussed in the
review by Eley and Cox (10).
The host-derived substances in GCF include antibodies, cytokines, enzymes and tissue degradation
products. The antibodies in gingival crevicular fluid
are comprised of both locally and systemically synthesized molecules and they reflect periodontal
colonization by particular microbial species. Antibodies are key players in the protection of the body

Fig. 1. Gingival crevice fluid a window to periodontal

disease. Gingival crevice fluid is composed of substances
derived from serum, leukocytes, bacteria, activated epithelial cells, connective tissue cells, and bone cells. Tissue
destruction during periodontal inflammation results in
production of tissue fragments and growth factors released from tissue stores. All these substances reflect the
periodontal disease process and can be potentially used
as indicators of periodontal condition.

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against pathogenic bacteria. However, they may also

be crucial in eliciting destructive inflammatory reactions in the periodontium. Antibodies in GCF and
strategies for using them to maintain local and systemic homeostasis are discussed in the issue by Ebersole (8).
Bone-specific markers such as the collagen telopeptide fragments and osteocalcin in GCF may reflect periodontal bone resorption. Giannobile et al.
review these factors in this volume (11). The article
by Champagne et al. explores the inflammatory mediator levels in subjects with periodontal diseases.
Their results suggest that some inflammatory mediator levels increase with time in periodontitis patients both in active and stable periodontal sites and
that the risk for periodontitis is related to the overall
systemic inflammatory response of an individual (5).
Proteolytic enzymes are released in periodontal
tissues during inflammation from leukocytes, activated structural cells of epithelium and connective
tissue. Of these enzymes, matrix metalloproteinases
(MMPs) have the main responsibility for degradation
of periodontal tissues. Recent studies have shown,
however, that MMPs also have specific functions in
controlling tissue defense reactions and repair. In an
attempt to find a specific MMP indicator for periodontal diseases focus should be directed to proteinases that are released during the active tissue destruction episodes of the diseases, rather than those
released from neutrophils throughout the inflammatory process. Also active rather than total (latent
plus active) enzyme activities should be measured.
Different techniques to measure host cell proteinases and interpretation of the results are discussed
in the article by Uitto et al. (23).
It is obvious that GCF provides a unique window
for analysis of periodontal condition. Collection of
GCF is a noninvasive and relatively simple procedure. The potential of GCF in early detection of
periodontitis and healing of periodontal tissues following therapy was already understood in the 1950s.
However, in the third year of the second millennium
we still do not have a practical and accurate periodontal indicator based on GCF. What are the barriers to their development? Periodontal diseases,
their microbial causes, cell regulation and tissue reactions during inflammation and healing have
proved to be extremely complex issues. We still do
not have a clear picture of the pathophysiological
events leading to tissue destruction connected to
periodontitis. We do not know the actual roles of different GCF enzymes in inflammation and tissue repair. We have only just started to understand the role

Introduction

of different pathogenic bacteria in the periodontitis

process. Several tests have been developed that are
aimed at specifically and sensitively revealing the
metabolic status of periodontal tissues. Some of
them have shown good specificity and sensitivity
values as well as potential for predicting disease progression. Unfortunately only a handful of GCF tests
have made their way into clinical practice. Clinicians
are still missing a practical test based on enzymes,
tissue degradation products or cytokines that accurately indicates an initial periodontitis process, active disease periods or effective healing. It is the
hope of this editor that the reviews in this volume of
Periodontology 2000 will serve as a stimulus for
studies resulting in further understanding of periodontal tissue physiology. This will eventually pave
the way for the development of practical GCF indicators that will aid in the accurate diagnosis and appropriate treatment of periodontal diseases.

9.

10.

11.

12.

13.
14.
15.

16.

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