Cytokine Profiles in Peripheral Blood and Whole Blood Cell Cultures Associated With Aggressive Periodontitis, Juvenile Idiopathic Arthritis, and Rheumatoid Arthritis Anne Havemose-Poulsen,* Lars Korsbæk Sørensen,* † Kaj Stoltze,* Klaus Bendtzen, † and Palle Holmstrup* Background: Cytokines play a key role in the pathogenesis of inflammatory diseases. An obvious question is whether patients with aggressive periodontitis, juvenile idiopathic arthritis, or rheu- matoid arthritis share blood cytokine profiles distinguishing them from individuals free of disease. Methods: The study population consisted of Danish white adults, <35 years of age, diagnosed with localized aggressive periodontitis (LAgP; N = 18), generalized aggressive periodontitis (GAgP; N = 27), juvenile idiopathic arthritis (JIA; N = 10), or rheu- matoid arthritis (RA; N = 23) and healthy individuals with no sys- temic or oral diseases (control [CTRL]; N = 25). Enzyme-linked immunosorbent assays were used to determine the levels of inter- leukin (IL)-1a, IL-1b, IL-1 receptor antagonist (IL-1Ra), IL-6, IL-10, tumor necrosis factor (TNF)-a, and lymphotoxin (LT)-a in peripheral blood (plasma) and unstimulated and stimulated whole blood cell cultures from the same blood collection. Autoantibodies (aAb) to IL-1a and IL-6 were quantitated by radioimmunoassay. Results: Similar patterns of slightly higher IL-10 levels in plasma were found for GAgP and RA patients and in unstimulated cultures for GAgP, RA, and JIA patients. Interestingly, unstimu- lated cultures also demonstrated similar patterns of higher TNF- a levels for these three groups of patients. Similar group patterns of periodontitis patients (LAgP and GAgP) included increased IL- 1Ra levels in stimulated cultures, which also showed similar group patterns of arthritis patients (JIA and RA) with respect to higher IL-1a and lower LT-a levels. Low titers of aAb to IL-1a and IL-6 were found in almost all individuals. Conclusion: Patients with aggressive periodontitis and types of arthritis presented with similar components of blood cytokine profiles distinguishing them from individuals free of disease. J Periodontol 2005;76:2276-2285. KEY WORDS Aggressive periodontitis; cell culture; cytokines; plasma; rheumatoid arthritis; white blood cell. I nflammatory diseases such as periodontitis and arthritis share some clinical characteristics in- cluding degradation of connective tissue and bone. 1,2 It is likely that the diseases include an increased risk of coexistence. 3-6 The extent to which patients with these diseases share immunoinflammatory charac- teristics, distinguishing them from individuals free of disease, is un- known. In the past two decades, evidence has been established for the involve- ment of pro- and anti-inflammatory cytokines in the pathogenesis of periodontitis, 7-9 juvenile idiopathic arthritis (JIA), 10-12 and rheumatoid arthritis (RA). 13-16 Numerous stud- ies have shown that the gingival crevicular fluid (GCF) and periodon- tal tissues of inflamed sites are rich in cytokines, 17-19 and roughly the same cytokines are found in the inflamed synovial membrane and synovial fluid in arthritides. 10,13,20 In general, however, it is uncertain whether patients with different types of periodontitis may be characterized by different systemic cytokine pat- terns and whether blood levels of cytokines may distinguish patients with periodontitis, JIA, and RA from healthy individuals. * Department of Periodontology, School of Dentistry, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark. † Institute for Inflammation Research, Rigshospitalet National University Hospital, Copenhagen, Copenhagen, Denmark. Volume 76 • Number 12 2276