Safoura Seifi - Department of oral and maxillofacial pathology, School of Dentistry, Babol University of Medical Sciences,Babol,Iran.
Ghorban Maliji - Department of Immunology, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran.
Mina Motallebnejad - Deparment of Oral Medicine, School of Dentistry, Babol University of Medical Sciences,Babol,Iran
Ehsan Maliji - Student Research Committee, Dental School, University of Medical Sciences, Babol, Iran.
Mahmood Khosravi Samani - Department of Periodontology, School of Dentistry, Babol University of Medical Sciences,Babol,Iran
Ramin Farokhi - Deparment of Oral Medicine, School of Dentistry, Babol University of Medical Sciences,Babol,Iran
Hesam Babaei - Department of Immunology, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran.

Background : Recurrent aphthous stomatitis (RAS) is one of the most common mucosal ulcerative of oral cavity. Role of immune system, especially cytokines in immunopathogenesis of aphthous stomatitis was not highly considered. The aim of this study was to evaluate the levels of salivary cytokines, including VEGF-R۳, TGF-&beta۱, TNF-&alpha, and IL-۱۷A/F in patients with RAS in two clinical stages, ulcerative and healing period. Material and Methods: In this case –control study, ۱۸ patients with RAS (case group) and ۱۸ healthy individuals (control groups) who were matched for age and sex, were selected. In both ulcerative and healing stages, unstimulated saliva of patients with RAS and healthy controls were collected. Levels of salivary cytokines, including VEGF-R۳, TGF-&beta, TNF-&alpha, and IL-۱۷A/F at each stage was determined by ELISA procedure and result were compared with the control group. Results: The levels of salivary VEGF-R۳ in the ulcerative (۵.۹۲ ۱.۸۷ng/ml) and healing (۷.۱۴ ±۳.۱ ng/ml) stages significantly decreased comparing with control group ( ۹.۷۱±۲.۲۴ ng/ml). Moreover, the level of salivary TGF-&beta۱ in ulcerative (۱۴۲.۲۱±۱۸.۷ pg/ml) and healing (۱۶۷.۰۲±۲۸.۱ pg/ml) stages significantly reduced comparing with control group (۱۷۸.۳۵±۵۵.۶۷ pg/ml). In addition, our finding showed that both inflammatory cytokines including TNF-&alpha and IL-۱۷ A/F significantly increased comparing to control group. The level of salivary TNF-&alpha in ulcerative (۳۴.۹±۱۱.۳۵pg/ml) and healing (۲۸.۰۹±۹.۰۷pg/ml) stages significantly increased comparing with control group (۱۰.۷۶±۱.۸۳ pg/ml). Also, the IL-۱۷ A/F level in the ulcerative  (۹۶.۴۴±۲۵.۷۴ pg/ml) and healing (۷۹.۱۷±۲۴.۹۶ pg/ml) stages significantly increased comparing to the control group (۵۳.۴۷±۱۳ pg/ml). Conclusion: Our finding in this study showed that the reduction of VEGF-R۳ and TGF-&beta۱ cytokines and increasing of inflammatory cytokines such as TNF-&alpha and IL-۱۷ A/F are effective in the pathogenesis of minor aphthous particularly in ulcerative stage. .

IL-۱۷A/F, Minor Aphthous, TGF-β۱, TNFα, Saliva, VEGF-R۳.