Volume 73 • Number 7 Level of Neopterin, a Marker of Immune Cell Activation in Gingival Crevicular Fluid, Saliva, and Urine in Patients With Aggressive Periodontitis Nurdan Ozmeriç,* Terken Baydar, † Ay¸ sen Bodur,* Ayse Basak Engin, † Ahu Uraz,* Kaya Eren,* and Gonul Sahin † 720 Background: Neopterin, a marker of cellular immune activation, is produced by human macrophages after induction by interferon gamma that is secreted by T lymphocytes. Neopterin concentrations in diverse body fluids have been reported to increase in parallel with bacteria in the clinical course of infections. Therefore, determination of neopterin in body fluids was thought to be useful for predicting the prognosis and diagnosis of aggressive forms of periodontal disease, in which the cell- mediated immune response plays an important role in immunopatho- genesis. The aim of the present study was to observe the role of neopterin in the pathogenesis of aggressive periodontitis (AgP). Methods: Thirteen individuals who were systemically and periodon- tally healthy and 16 systemically healthy individuals diagnosed with AgP were recruited for this study. Mixed saliva and urine samples were collected from each subject. Gingival crevicular fluid (GCF) samples were obtained from 6 teeth with ≥5 mm probing depth (PD). After eval- uation of GCF amount from paper strips, enzyme-linked immunosorbent assay (ELISA) was employed to determine the amount of neopterin in urine, saliva, and GCF. Results: The amount of neopterin in urine and saliva measured 235.77 ± 405.31 μmol neopterin/mol creatinine and 9.85 ± 7.66 nmol/l, respectively, for the AgP group and 225.45 ± 100.72 μmol neopterin/mol creatinine and 5.25 ± 5.76 nmol/l, respectively, for controls. The pres- ent data demonstrate that, while salivary neopterin levels were found to be significantly different between periodontitis and control subjects, there were non-significant differences in urine neopterin levels. The amount and concentration of neopterin in GCF measured was 18 ± 12.75 nmol/l and 3.67 ± 2.40 nmol/ml for the AgP group and 2.51 ± 1.72 nmol/l and 3.88 ± 4.50 nmol/ml for the control group. When total amounts of neopterin are taken into consideration, a significant differ- ence between AgP and controls is shown; however, no significant dif- ference in net concentration of neopterin was found between both groups. Conclusions: This study is the first report to evaluate the involvement of neopterin in AgP and this might be considered of value in under- standing periodontal disease mechanisms. J Periodontol 2002;73:720-725. KEY WORDS Gingival crevicular fluid; neopterin; periodontitis, aggressive/ pathogenesis; saliva/analysis; urine/analysis. * Department of Periodontology, Faculty of Dentistry, Gazi University, Ankara, Turkey. † Department of Toxicology, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey. N eopterin, an actual molecu- lar mass compound belong- ing to the class of pteridines, is an early and valuable biomarker of cellular immunity. Increased lev- els of neopterin in some body fluids have been observed in a number of diseases including cellular immu- nity, such as allograft rejection, autoimmune diseases (Behcet’s dis- ease, rheumatoid arthritis, etc.), viral infections, and certain malignant disorders (solid tumors, hematolog- ical malignancies, etc.). 1-8 Neopterin is a metabolite of guanosine triphos- phate (GTP), and in vitro interferon- gamma (IFN-γ) is the only cytokine that induces production of large amounts of neopterin in cell culture supernatants. However, in human monocytes/macrophages and in some human cell lines stimulated with this cytokine, neopterin is pro- duced and released instead of other pteridine derivatives (Fig. 1). 5-8 Neopterin is biologically stable and can be easily quantified in human body fluids and its concen- trations in serum and in urine increase in parallel to the clinical course of infections with viruses, intracellular bacteria, and para- sites. 2,3,7 A number of studies eval- uated the neopterin status in vari- ous human biological fluids, but not GCF. Saliva and GCF contain both host and microbial-derived factors, including several enzymes and cytokines. 9-11