Review article Cytokine profile in the synovial fluid of patients with temporomandibular joint disorders: A systematic review Sergio Varela Kellesarian a , Abdulaziz A. Al-Kheraif b , Fahim Vohra c , Alexis Ghanem a , Hans Malmstrom a , Georgios E. Romanos a,d , Fawad Javed a,⇑ a Division of General Dentistry, Eastman Institute for Oral Health, University of Rochester, NY, USA b Dental Health Department, College of Applied Medical Sciences, King Saud University, Riyadh 11541, Saudi Arabia c Department of Prosthetic Dental Sciences, College of Dentistry, King Saud University, Riyadh, Saudi Arabia d Department of Periodontology, School of Dental Medicine, Stony Brook University, NY, USA article info Article history: Received 29 September 2015 Received in revised form 23 October 2015 Accepted 2 November 2015 Keywords: Cytokine Temporomandibular joint Disorder Synovial fluid Inflammation abstract The aim of this study was to review the cytokine profiles in the synovial fluid (SF) of patients with tem- poromandibular joint disorders (TMJD). Databases were searched from 1965 till September 2015 using different combinations of the following key words: ‘‘Temporomandibular joint”; ‘‘Cytokine”; ‘‘disorder”; and ‘‘synovial fluid” and ‘‘inflammation”. Titles and abstracts of studies identified using the above- described protocol were screened and checked for agreement. Full-texts of articles judged by title and abstract to be relevant were read and independently evaluated. Hand-searching of the reference lists of potentially relevant original and review articles was also performed. The pattern of the present sys- tematic review was customized to mainly summarize the relevant data. Fifteen studies were included. In 12 studies, cytokine profile of patients with TMJD was assessed using enzyme linked immunosorbent assay; and in 2 studies, histological analysis was performed to assess the cytokine profile of patients with TMJD. Patients with TMJD presented raised levels of interleukin (IL)-6 in 8 studies, IL-1beta (1b) in 5 studies and tumor necrosis factor-alpha (TNF-a) in 5 studies. Two studies showed no significant difference in TNF-a levels in patients with and without TMJD; and IL-1b levels were comparable in patients with and without TMJD in 2 studies. Raised levels of IL-6, TNF-a, IL-1b, IL-8, and IFN-c in the SF have been associated with inflammation in patients with TMJD. Cytokines IL-10, osteoclastogenesis inhibitory factor/osteoprotegerin (OCIF/OPG), and VEGF found in the SF of TMJs could have an anti-inflammatory effect. Ó 2015 Published by Elsevier Ltd. Contents 1. Introduction .......................................................................................................... 99 2. Materials and methods ................................................................................................. 99 2.1. Focused question ................................................................................................. 99 2.2. Eligibility criteria ................................................................................................. 99 2.3. Search strategy and study selection .................................................................................. 99 2.4. Methodological study quality assessment ............................................................................. 99 3. Results.............................................................................................................. 100 3.1. Characteristics of included studies .................................................................................. 100 3.1.1. General characteristics .................................................................................... 100 3.1.2. Methods for the assessment of cytokines ..................................................................... 100 3.1.3. Interleukin-6 ............................................................................................ 100 http://dx.doi.org/10.1016/j.cyto.2015.11.005 1043-4666/Ó 2015 Published by Elsevier Ltd. ⇑ Corresponding author at: Division of General Dentistry, Eastman Institute for Oral Health, 625 Elmwood Avenue, University of Rochester, Rochester, NY 14620, USA. E-mail address: Fawad_Javed@urmc.rochester.edu (F. Javed). Cytokine 77 (2016) 98–106 Contents lists available at ScienceDirect Cytokine journal homepage: www.journals.elsevier.com/cytokine