Basic Research| Volume 41, ISSUE 3, P358-362, March 2015

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Periapical Cytokine Expression in Sickle Cell Disease

Published:January 06, 2015DOI:



      Sickle cell anemia (SCA) is the most prevalent genetic disease worldwide. Patients with SCA exhibit increased levels of proinflammatory mediators as part of a permanently activated immunoinflammatory status.


      The aim of this study was to evaluate the mRNA expression levels of the cytokines interferon (IFN-γ), tumor necrosis factor, interleukin (IL-1β, IL-17A, IL-10), receptor activator for nuclear factor kappa B ligand, and the chemokines CCL2/MCP-1 and CCL5 in the periapical interstitial fluid from SCA individuals compared with healthy individuals. Samples were collected from 12 teeth of SCA patients and 12 non-SCA patients with apical periodontitis. In addition, 12 teeth were sampled from the periapical region of healthy patients with vital pulp (control). The expression of cytokine mRNA was detected by using real-time polymerase chain reaction.


      The expression of mRNA for the Th1-associated cytokines IFN-γ, tumor necrosis factor-α, and IL-1β were significantly higher in SCA individuals than in the control individuals (P < .05). Among Th1-associated cytokines, only IFN-γ was significantly increased in non-SCA compared with control patients (vital pulp). The expression of IL-17A mRNA was significant higher in SCA cases than in control samples (P < .05), whereas the IL-10 mRNA expression was significantly increased in SCA and non-SCA individuals when compared with the control group. Similar levels of receptor activator for nuclear factor kappa B ligand, CCL2, and CCL5 mRNA expression were observed in all samples. However, no significant differences were observed in the expression of cytokine or chemokine mRNA between SCA and non-SCA individuals (P > .05).


      The results were able to demonstrate that SCA patients presented prone proinflammatory ability, despite the fact that any differences in periapical immune responses between SCA and non-SCA individuals were not observed.

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        • Stashenko P.
        • Yu S.M.
        • Wang C.Y.
        Kinetics of immune cell and bone resorptive responses to endodontic infections.
        J Endod. 1992; 18: 422-426
        • Takahashi K.
        Microbiological, pathological, inflammatory, immunological and molecular biological aspects of periradicular disease.
        Int Endod J. 1998; 31: 311-325
        • Marton I.J.
        • Rot A.
        • Schwarzinger E.
        • et al.
        Differential in situ distribution of interleukin-8, monocyte chemoattractant protein-1 and Rantes in human chronic periapical granuloma.
        Oral Microbiol Immunol. 2000; 15: 63-65
        • Fukada S.Y.
        • Silva T.A.
        • Garlet G.P.
        • et al.
        Factors involved in the T helper type 1 and type 2 cell commitment and osteoclast regulation in inflammatory apical diseases.
        Oral Microbiol Immunol. 2009; 24: 25-31
        • Eyerich S.
        • Eyerich K.
        • Cavani A.
        • Schmidt-Weber C.
        IL-17 and IL-22: siblings, not twins.
        Trends Immunol. 2010; 31: 354-361
        • Henriques L.C.
        • de Brito L.C.
        • Tavares W.L.
        • et al.
        Cytokine analysis in lesions refractory to endodontic treatment.
        J Endod. 2011; 37: 1659-1662
      1. World Health Organization. Sickle cell anemia: report of secretariat. 59th World of Health Assembly. Available at: http// Accessed January 1, 2013.

        • Miller R.G.
        • Segal J.B.
        • Ashar B.H.
        • et al.
        High prevalence and correlates of low bone mineral density in young adults with sickle cell disease.
        Am J Hematol. 2006; 81: 236-241
        • Rees D.C.
        • Williams T.N.
        • Gladwin M.T.
        Sickle-cell disease.
        Lancet. 2010; 376: 2018-2031
        • Demirbas Kaya A.
        • Aktener B.O.
        • Unsal C.
        Pulpal necrosis with sickle cell anaemia.
        Int Endod J. 2004; 37: 602-606
        • Costa C.P.
        • Thomaz E.B.
        • Souza Sde F.
        Association between sickle cell anemia and pulp necrosis.
        J Endod. 2013; 39: 177-181
        • Pathare A.
        • Kindi S.A.
        • Daar S.
        • Dennison D.
        Cytokines in sickle cell disease.
        Hematology. 2003; 8: 329-337
        • Veiga P.C.
        • Schroth R.J.
        • Guedes R.
        • et al.
        Serum cytokine profile among Brazilian children of African descent with periodontal inflammation and sickle cell anaemia.
        Arch Oral Biol. 2013; 58: 505-510
        • Tavares W.L.
        • de Brito L.C.
        • Henriques L.C.
        • et al.
        Effects of calcium hydroxide on cytokine expression in endodontic infections.
        J Endod. 2012; 38: 1368-1371
        • de Brito L.C.
        • Teles F.R.
        • Teles R.P.
        • et al.
        T-lymphocyte and cytokine expression in human inflammatory periapical lesions.
        J Endod. 2012; 38: 481-485
        • Tavares W.L.
        • de Brito L.C.
        • Henriques L.C.
        • et al.
        The impact of chlorhexidine-based endodontic treatment on periapical cytokine expression in teeth.
        J Endod. 2013; 39: 889-892
        • Barbosa Silva M.J.
        • Vieira L.Q.
        • Sobrinho A.P.
        The effects of mineral trioxide aggregates on cytokine production by mouse pulp tissue.
        Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2008; 105: e70-e76
        • Schmittgen T.D.
        • Livak K.J.
        Analyzing real-time PCR data by the comparative C(T) method.
        Nat Protoc. 2008; 3: 1101-1108
        • de Carvalho Fraga C.A.
        • Alves L.R.
        • de Sousa A.A.
        • et al.
        Th1 and Th2-like protein balance in human inflammatory radicular cysts and periapical granulomas.
        J Endod. 2013; 39: 453-455
        • Jison M.L.
        • Munson P.J.
        • Barb J.J.
        • et al.
        Blood mononuclear cell gene expression profiles characterize the oxidant, hemolytic, and inflammatory stress of sickle cell disease.
        Blood. 2004; 104: 270-280
        • Chang Y.C.
        • Yang S.F.
        • Huang F.M.
        • et al.
        Induction of tissue plasminogen activator gene expression by proinflammatory cytokines in human pulp and gingival fibroblasts.
        J Endod. 2003; 29: 114-117
        • Prso I.B.
        • Kocjan W.
        • Simic H.
        • et al.
        Tumor necrosis factor-alpha and interleukin 6 in human periapical lesions.
        Mediators Inflamm. 2007; 2007: 38210
        • Silva T.A.
        • Garlet G.P.
        • Lara V.S.
        • et al.
        Differential expression of chemokines and chemokine receptors in inflammatory periapical diseases.
        Oral Microbiol Immunol. 2005; 20: 310-316
        • Hernadi K.
        • Gyongyosi E.
        • Meszaros B.
        • et al.
        Elevated tumor necrosis factor-alpha expression in periapical lesions infected by Epstein-Barr virus.
        J Endod. 2013; 39: 456-460
        • Burgener B.
        • Ford A.R.
        • Situ H.
        • et al.
        Biologic markers for odontogenic periradicular periodontitis.
        J Endod. 2010; 36: 1307-1310
        • Stashenko P.
        • Teles R.
        • D'Souza R.
        Periapical inflammatory responses and their modulation.
        Crit Rev Oral Biol Med. 1998; 9: 498-521
        • Nair P.N.
        Pathogenesis of apical periodontitis and the causes of endodontic failures.
        Crit Rev Oral Biol Med. 2004; 15: 348-381
        • Sasaki H.
        • Balto K.
        • Kawashima N.
        • et al.
        Gamma interferon (IFN-gamma) and IFN-gamma-inducing cytokines interleukin-12 (IL-12) and IL-18 do not augment infection-stimulated bone resorption in vivo.
        Clin Diagn Lab Immunol. 2004; 11: 106-110
        • Colic M.
        • Gazivoda D.
        • Vucevic D.
        • et al.
        Regulatory T-cells in periapical lesions.
        J Dent Res. 2009; 88: 997-1002
        • Oseko F.
        • Yamamoto T.
        • Akamatsu Y.
        • et al.
        IL-17 is involved in bone resorption in mouse periapical lesions.
        Microbiol Immunol. 2009; 53: 287-294
        • Menezes R.
        • Bramante C.M.
        • da Silva Paiva K.B.
        • et al.
        Receptor activator NFkappaB-ligand and osteoprotegerin protein expression in human periapical cysts and granulomas.
        Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006; 102: 404-409
        • Colic M.
        • Gazivoda D.
        • Vucevic D.
        • et al.
        Proinflammatory and immunoregulatory mechanisms in periapical lesions.
        Mol Immunol. 2009; 47: 101-113
        • Marcal J.R.
        • Samuel R.O.
        • Fernandes D.
        • et al.
        T-helper cell type 17/regulatory T-cell immunoregulatory balance in human radicular cysts and periapical granulomas.
        J Endod. 2010; 36: 995-999
        • Chensue S.W.
        • Warmington K.S.
        • Allenspach E.J.
        • et al.
        Differential expression and cross-regulatory function of RANTES during mycobacterial (type 1) and schistosomal (type 2) antigen-elicited granulomatous inflammation.
        J Immunol. 1999; 163: 165-173
        • AlShwaimi E.
        • Purcell P.
        • Kawai T.
        • et al.
        Regulatory T cells in mouse periapical lesions.
        J Endod. 2009; 35: 1229-1233