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Pro-inflammatory interleukins in middle ear effusions from atopic and non-atopic children with chronic otitis media with effusion

  • Otology
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Abstract

Chronic otitis media with effusion (OME) is associated with irreversible changes in the middle ear, sometimes leading to hearing loss and abnormal language development in children. While the pathogenesis of OME is not fully understood, inflammatory and allergic factors are thought to be involved. The study aimed to investigate the role of cytokines in the local development of chronic OME, and assess differences in the cytokine profiles between atopic and non-atopic children. 84 atopic and non-atopic children with chronic OME (mean age of 6 years 7 months) were studied. Age-matched children with hypertrophy of the adenoids and Eustachian tube dysfunction served as the control group. The number of past acute otitis media (AOM) episodes, their age, and the type of effusion were recorded for all children. Pro-inflammatory cytokine concentrations (TNF-α, IL-1β, IL-6 and IL-8) were determined and the presence of pathogenic bacteria in the patients’ effusions was examined. High concentrations of TNF-α, IL-1β, IL-6 and IL-8 were found in the effusions in all children with chronic OME, with the highest levels observed in the non-atopic group. The atopic group showed persistently high IL-1β levels, while in the non-atopic children, IL-1β and TNF-α levels positively correlated with the patient’s age and the number of past AOM episodes. Pathogenic bacteria were more frequently isolated from effusions in non-atopic children. In both atopic and non-atopic children, pro-inflammatory cytokines are found at high concentrations. This argues in favor of instituting anti-inflammatory management for treating OME, regardless of atopy.

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References

  1. Bluestone CD, Klein JO (1995) Clinical practice guideline on otitis media with effusion in young children: strengths and weaknesses. Otolaryngol Head Neck Surg 112:507–511

    CAS  PubMed  Google Scholar 

  2. Lieberthal AS, Carroll AE, Chonmaitree T, Ganiats TG, Hoberman A, Jackson MA, Joffe MD, Miller DT, Rosenfeld RM, Sevilla XD, Schwartz RH, Thomas PA, Tunkel DE (2013) The diagnosis and management of acute otitis media. Pediatrics 131:e964–e999

    Article  PubMed  Google Scholar 

  3. Qureishi A, Lee Y, Belfield K, Birchall JP, Daniel M (2014) Update on otitis media—prevention and treatment. Infect Drug Resist 7:15–24

    PubMed  PubMed Central  Google Scholar 

  4. Bluestone CD, Hebda PA, Alper CM, Sando I, Buchman CA, Stangerup SE, Felding JU, Swarts JD, Ghadiali SN, Takahashi H (2005) Recent advances in otitis media. 2. Eustachian tube, middle ear, and mastoid anatomy; physiology, pathophysiology, and pathogenesis. Ann Otol Rhinol Laryngol Suppl 194:16–30

    PubMed  Google Scholar 

  5. Amin K, Hurst DS, Roomans GM, Venge P, Sevéus L (1999) Eosinophils and neutrophils in biopsies from the middle ear of atopic children with otitis media with effusion. Inflamm Res 48:626–631

    Article  CAS  PubMed  Google Scholar 

  6. Armstrong BW (1954) A new treatment for chronic secretory otitis media. AMA Arch Otolaryngol 59:653–654

    Article  CAS  PubMed  Google Scholar 

  7. Ball SS, Prazma J, Dais CG, Triana RJ, Pillsbury HC (1997) Role of tumor necrosis factor and interleukin-1 in endotoxin-induced middle ear effusions. Ann Otol Rhinol Laryngol 106:633–639

    Article  CAS  PubMed  Google Scholar 

  8. Bernstein JM (1996) Role of allergy in eustachian tube blockage and otitis media with effusion: a review. Otolaryngol Head Neck Surg 114:562–568

    Article  CAS  PubMed  Google Scholar 

  9. Buchman CA, Doyle WJ, Skoner DP, Post JC, Alper CM, Seroky JT, Anderson K, Preston RA, Hayden FG, Fireman P et al (1995) Influenza A virus-induced acute otitis media. J Infect Dis 172:1348–1351

    Article  CAS  PubMed  Google Scholar 

  10. Sato K, Liebeler CL, Quartey MK, Le CT, Giebink GS (1999) Middle ear fluid cytokine and inflammatory cell kinetics in the chinchilla otitis media model. Infect Immun 67:1943–1946

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Yariktas M, Doner F, Dogru H, Yasan H, Delibas N (2004) The role of free oxygen radicals on the development of otitis media with effusion. Int J Pediatr Otorhinolaryngol 68:889–894

    Article  PubMed  Google Scholar 

  12. Aydoğan B, Kiroğlu M, Altintas D, Yilmaz M, Yorgancilar E, Tuncer U (2004) The role of food allergy in otitis media with effusion. Otolaryngol Head Neck Surg 130:747–750

    Article  PubMed  Google Scholar 

  13. Döner F, Yariktas M, Demirci M (2004) The role of allergy in recurrent otitis media with effusion. J Invest Allergol Clin Immunol 14:154–158

    Google Scholar 

  14. Nsouli TM, Nsouli SM, Linde RE, O’Mara F, Scanlon RT, Bellanti JA (1994) Role of food allergy in serous otitis media. Ann Allergy 73:215–219

    CAS  PubMed  Google Scholar 

  15. Pelikan Z (2009) Role of nasal allergy in chronic secretory otitis media. Curr Allergy Asthma Rep 9:107–113

    Article  PubMed  Google Scholar 

  16. Hurst DS, Venge P (2002) The impact of atopy on neutrophil activity in middle ear effusion from children and adults with chronic otitis media. Arch Otolaryngol Head Neck Surg 128:561–566

    Article  PubMed  Google Scholar 

  17. Luong A, Roland PS (2008) The link between allergic rhinitis and chronic otitis media with effusion in atopic patients. Otolaryngol Clin North Am 41:311–323

    Article  PubMed  Google Scholar 

  18. Lin J, Vambutas A, Haruta A, Paparella MM, Giebink GS, Kim Y (1999) Pneumococcus activation of the 5-lipoxygenase pathway and production of glycoproteins in the middle ear of rats. J Infect Dis 179:1145–1151

    Article  CAS  PubMed  Google Scholar 

  19. Dinarello CA (2000) Proinflammatory cytokines. Chest 118:503–508

    Article  CAS  PubMed  Google Scholar 

  20. Barzilai A, Dekel B, Dagan R, Passwell JH, Leibovitz E (1999) Cytokine analysis of middle ear effusions during acute otitis media: significant reduction in tumor necrosis factor alpha concentrations correlates with bacterial eradication. Pediatr Infect Dis J 18:301–303

    Article  CAS  PubMed  Google Scholar 

  21. Himi T, Suzuki T, Kodama H, Takezawa H, Kataura A (1992) Immunologic characteristics of cytokines in otitis media with effusion. Ann Otol Rhinol Laryngol Suppl 157:21–25

    CAS  PubMed  Google Scholar 

  22. Lin J, Kim Y, Juhn SK (1998) Increase of mucous glycoprotein secretion by tumor necrosis factor alpha via a protein kinase C-dependent mechanism in cultured chinchilla middle ear epithelial cells. Ann Otol Rhinol Laryngol 107:213–219

    Article  CAS  PubMed  Google Scholar 

  23. Nell MJ, Grote JJ (1999) Endotoxin and tumor necrosis factor-alpha in middle ear effusions in relation to upper airway infection. Laryngoscope 109:1815–1819

    Article  CAS  PubMed  Google Scholar 

  24. Ondrey FG, Juhn SK, Adams GL (1998) Early-response cytokine expression in adult middle ear effusions. Otolaryngol Head Neck Surg 119:342–345

    Article  CAS  PubMed  Google Scholar 

  25. Ophir D, Hahn T, Schattner A, Wallach D, Aviel A (1988) Tumor necrosis factor in middle ear effusions. Arch Otolaryngol Head Neck Surg 114:1256–1258

    Article  CAS  PubMed  Google Scholar 

  26. Smirnova MG, Kiselev SL, Gnuchev NV, Birchall JP, Pearson JP (2002) Role of the pro-inflammatory cytokines tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6 and interleukin-8 in the pathogenesis of the otitis media with effusion. Eur Cytokine Netw 13:161–172

    CAS  PubMed  Google Scholar 

  27. Yellon RF, Doyle WJ, Whiteside TL, Diven WF, March AR, Fireman P (1995) Cytokines, immunoglobulins, and bacterial pathogens in middle ear effusions. Arch Otolaryngol Head Neck Surg 121:865–869

    Article  CAS  PubMed  Google Scholar 

  28. Yellon RF, Leonard G, Marucha PT, Craven R, Carpenter RJ, Lehmann WB, Burleson JA, Kreutzer DL (1991) Characterization of cytokines present in middle ear effusions. Laryngoscope 101:165–169

    Article  CAS  PubMed  Google Scholar 

  29. Jeon EJ, Park YS, Choi YC, Yeo SW, Jung TT (2001) Effect of inhibitor of tumor necrosis factor-alpha on experimental otitis media with effusion. Ann Otol Rhinol Laryngol 110:917–921

    Article  CAS  PubMed  Google Scholar 

  30. Hebda PA, Alper CM, Doyle WJ, Burckart GJ, Diven WF, Zeevi A (1998) Upregulation of messenger RNA for inflammatory cytokines in middle ear mucosa in a rat model of acute otitis media. Ann Otol Rhinol Laryngol 107:501–507

    Article  CAS  PubMed  Google Scholar 

  31. Johnson MD, Fitzgerald JE, Leonard G, Burleson JA, Kreutzer DL (1994) Cytokines in experimental otitis media with effusion. Laryngoscope 104:191–196

    Article  CAS  PubMed  Google Scholar 

  32. Sato K, Kawana M, Nonomura N, Nakano Y (1999) Course of IL-1beta, IL-6, IL-8, and TNF-alpha in the middle ear fluid of the guinea pig otitis media model induced by nonviable Haemophilus influenzae. Ann Otol Rhinol Laryngol 108:559–563

    Article  CAS  PubMed  Google Scholar 

  33. Kawano H, Haruta A, Tsuboi Y, Kim Y, Schachern PA, Paparella MM, Lin J (2002) Induction of mucous cell metaplasia by tumor necrosis factor alpha in rat middle ear: the pathological basis for mucin hyperproduction in mucoid otitis media. Ann Otol Rhinol Laryngol 111:415–422

    Article  PubMed  Google Scholar 

  34. Smirnova MG, Birchall JP, Pearson JP (2004) The immunoregulatory and allergy-associated cytokines in the aetiology of the otitis media with effusion. Mediators Inflamm 13:75–88

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Lee HY, Chung JH, Lee SK, Byun JY, Kim YI, Yeo SG (2013) Toll-like receptors, cytokines and nitric oxide synthase in patients with otitis media with effusion. Indian J Med Res 138:523–530

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Lee DH, Park YS, Jung TT, Yeo SW, Choi YC, Jeon E (2001) Effect of tumor necrosis factor-alpha on experimental otitis media with effusion. Laryngoscope 111:728–733

    Article  CAS  PubMed  Google Scholar 

  37. Lin J, Haruta A, Kawano H, Ho SB, Adams GL, Juhn SK, Kim Y (2000) Induction of mucin gene expression in middle ear of rats by tumor necrosis factor-alpha: potential cause for mucoid otitis media. J Infect Dis 182:882–887

    Article  CAS  PubMed  Google Scholar 

  38. Johnson MD, Contrino A, Contrino J, Maxwell K, Leonard G, Kreutzer D (1994) Murine model of otitis media with effusion: immunohistochemical demonstration of IL-1 alpha antigen expression. Laryngoscope 104:1143–1149

    Article  CAS  PubMed  Google Scholar 

  39. DeMaria TF, Briggs BR, Lim DJ, Okazaki N (1984) Experimental otitis media with effusion following middle ear inoculation of nonviable H. influenzae. Ann Otol Rhinol Laryngol 93:52–56

    Article  CAS  PubMed  Google Scholar 

  40. Catanzaro A, Ryan A, Batcher S, Wasserman SI (1991) The response to human rIL-1, rIL-2, and rTNF in the middle ear of guinea pigs. Laryngoscope 101:271–275

    Article  CAS  PubMed  Google Scholar 

  41. Hunter SE, Singla AK, Prazma J, Jewett BS, Randell SH, Pillsbury HC 3rd (1999) Mucin production in the middle ear in response to lipopolysaccharides. Otolaryngol Head Neck Surg 120:884–888

    Article  CAS  PubMed  Google Scholar 

  42. Forseni M, Bagger-Sjöbäck D, Hultcrantz M (2001) A study of inflammatory mediators in the human tympanosclerotic middle ear. Arch Otolaryngol Head Neck Surg 127:559–564

    Article  CAS  PubMed  Google Scholar 

  43. Watanabe T, Hirano T, Suzuki M, Kurono Y, Mogi G (2001) Role of interleukin-1beta in a murine model of otitis media with effusion. Ann Otol Rhinol Laryngol 110:574–580

    Article  CAS  PubMed  Google Scholar 

  44. Park MK, Lee BD (2013) Development of animal models of otitis media. Korean J Audiol 17:9–12

    Article  PubMed  PubMed Central  Google Scholar 

  45. DeMaria TF, Murwin DM (1997) Tumor necrosis factor during experimental lipopolysaccharide-induced otitis media. Laryngoscope 107:369–372

    Article  CAS  PubMed  Google Scholar 

  46. DeMaria TF, Prior RB, Briggs BR, Lim DJ, Birck HG (1984) Endotoxin in middle-ear effusions from patients with chronic otitis media with effusion. J Clin Microbiol 20:15–17

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Johnson M, Leonard G, Kreutzer DL (1997) Murine model of interleukin-8-induced otitis media. Laryngoscope 107:1405–1408

    Article  CAS  PubMed  Google Scholar 

  48. Willett DN, Rezaee RP, Billy JM, Tighe MB, DeMaria TF (1998) Relationship of endotoxin to tumor necrosis factor-alpha and interleukin-1 beta in children with otitis media with effusion. Ann Otol Rhinol Laryngol 107:28–33

    Article  CAS  PubMed  Google Scholar 

  49. Barzilaia A, Dekel B, Dagan R, Leibovitz E (2000) Middle ear effusion IL-6 concentration in bacterial and non-bacterial acute otitis media. Acta Paediatr 89:1068–1071

    Article  CAS  PubMed  Google Scholar 

  50. Hebert CA, Baker JB (1993) Interleukin-8: a review. Cancer Invest 11:743–750

    Article  CAS  PubMed  Google Scholar 

  51. Kuna P, Lazarovich M, Kaplan AP (1996) Chemokines in seasonal allergic rhinitis. J Allergy Clin Immunol 97:104–112

    Article  CAS  PubMed  Google Scholar 

  52. Tchorzewski H, Krasomski G, Biesiada L, Głowacka E, Banasik M, Lewkowicz P (2000) IL-12, IL-6 and IFN-gamma production by lymphocytes of pregnant women with rheumatoid arthritis remission during pregnancy. Mediators Inflamm 9:289–293

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. MacArthur CJ, Pillers DA, Pang J, Kempton JB, Trune DR (2011) Altered expression of middle and inner ear cytokines in mouse otitis media. Laryngoscope 121:365–371

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Kubba H, Pearson JP, Birchall JP (2000) The aetiology of otitis media with effusion: a review. Clin Otolaryngol Allied Sci 25:181–194

    Article  CAS  PubMed  Google Scholar 

  55. Kubba H (2000) An evidence-based patient information leaflet about otitis media with effusion. Clin Perform Qual Health Care 8:93–99

    Article  CAS  PubMed  Google Scholar 

  56. Ogra PL, Giebink GS, Barenkamp SJ, DeMaria TF, Juhn SK, Shurin PA, Andersson B, Bakaletz LO, Bernstein JM, Brinton CC et al (1989) Recent advances in otitis media. Microbiology, immunology, biochemistry, and vaccination. Ann Otol Rhinol Laryngol Suppl 139:23–32

    CAS  PubMed  Google Scholar 

  57. Fergie N, Bayston R, Pearson JP, Birchall JP (2004) Is otitis media with effusion a biofilm infection? Clin Otolaryngol Allied Sci 29:38–46

    Article  CAS  PubMed  Google Scholar 

  58. Giebink GS (1989) Progress in understanding the pathophysiology of otitis media. Pediatr Rev 11:133–137

    Article  CAS  PubMed  Google Scholar 

  59. Juhn SK, Giebink GS, Huff JS, Mills EL (1980) Biochemical and immunochemical characteristics of middle ear effusions in relation to bacteriological findings. Ann Otol Rhinol Laryngol Suppl 89:161–167

    CAS  PubMed  Google Scholar 

  60. Pereira MB, Pereira MR, Cantarelli V, Costa SS (2004) Prevalence of bacteria in children with otitis media with effusion. J Pediatr (Rio J) 80:41–48

    Article  Google Scholar 

  61. Chung MH, Griffith SR, Park KH, Lim DJ, DeMaria TF (1993) Cytological and histological changes in the middle ear after inoculation of influenza A virus. Acta Otolaryngol 113:81–87

    Article  CAS  PubMed  Google Scholar 

  62. Yellon RF, Leonard G, Marucha P, Sidman J, Carpenter R, Burleson J, Carlson J, Kreutzer D (1992) Demonstration of interleukin 6 in middle ear effusions. Arch Otolaryngol Head Neck Surg 118:745–748

    Article  CAS  PubMed  Google Scholar 

  63. Juhn SK, Tolan CT, Garvis WJ, Cross DS, Giebink GS (1992) The levels of IL-1 beta in human middle ear effusions. Acta Otolaryngol Suppl 493:37–42

    CAS  PubMed  Google Scholar 

  64. Yetiser S, Satar B, Gumusgun A, Unal F, Ozkaptan Y (2002) Tumor necrosis factor-alpha and interleukin-1beta levels in recurrent and persistent otitis media with effusion. Otolaryngol Head Neck Surg 126:417–422

    Article  PubMed  Google Scholar 

  65. Ciprandi G, Buscaglia S, Pesce G, Pronzato C, Ricca V, Parmiani S, Bagnasco M, Canonica GW (1995) Minimal persistent inflammation is present at mucosal level in patients with asymptomatic rhinitis and mite allergy. J Allergy Clin Immunol 96:971–979

    Article  CAS  PubMed  Google Scholar 

  66. Skotnicka B, Hassmann E (2000) Cytokines in children with otitis media with effusion. Eur Arch Otorhinolaryngol 257:323–326

    Article  CAS  PubMed  Google Scholar 

  67. Maxwell KS, Fitzgerald JE, Burleson JA, Leonard G, Carpenter R, Kreutzer DL (1994) Interleukin-8 expression in otitis media. Laryngoscope 104:989–995

    Article  CAS  PubMed  Google Scholar 

  68. Russo E, Smith CW, Friedman EM, Smith EO, Kaplan SL (2004) Cell adhesion molecules and cytokines in middle ear effusions in children with or without recent acute otitis media. Otolaryngol Head Neck Surg 130:242–248

    Article  PubMed  Google Scholar 

  69. Kerschner JE, Meyer TK, Yang C, Burrows A (2004) Middle ear epithelial mucin production in response to interleukin-6 exposure in vitro. Cytokine 26:30–36

    Article  CAS  PubMed  Google Scholar 

  70. Smirnova MG, Birchall JP, Pearson JP (2002) In vitro study of IL-8 and goblet cells: possible role of IL-8 in the aetiology of otitis media with effusion. Acta Otolaryngol 122:146–152

    Article  CAS  PubMed  Google Scholar 

  71. Bachert C, van Kempen M, Van Cauwenberge P (1999) Regulation of proinflammatory cytokines in seasonal allergic rhinitis. Int Arch Allergy Immunol 118:375–379

    Article  CAS  PubMed  Google Scholar 

  72. Al-Amran FG, Hadi NR, Hashim AM (2013) Cysteinyl leukotriene receptor antagonist montelukast ameliorates acute lung injury following haemorrhagic shock in rats. Eur J Cardiothorac Surg 43:421–427

    Article  PubMed  Google Scholar 

  73. Lee HY, Kim YI, Lee JW, Byun JY, Park MS, Yeo SG (2013) Decreased expression of TLR-9 and cytokines in the presence of bacteria in patients with otitis media with effusion. Clin Exp Otorhinolaryngol 6:195–200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Matkovic SD, Vojvodić D, Baljosevic I (2007) Cytokine levels in groups of patients with different duration of chronic secretory otitis. Eur Arch Otorhinolaryngol 264:1283–1287

    Article  PubMed  Google Scholar 

  75. Park YS, Auo HJ, Jeon EJ, Chang KH, Lee SK, Lee DH (2006) Effect of inhibitor of tumor necrosis factor-alpha and oxatomide on immune mediated otitis media. Laryngoscope 116:1642–1646

    Article  CAS  PubMed  Google Scholar 

  76. Kim DH, Park YS, Jeon EJ, Yeo SW, Chang KH, Lee SK (2006) Effects of tumor necrosis factor alpha antagonist, platelet activating factor antagonist, and nitric oxide synthase inhibitor on experimental otitis media with effusion. Ann Otol Rhinol Laryngol 115:617–623

    Article  PubMed  Google Scholar 

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Conflict of interest

The authors declare that they have no conflict of interest. The technical and language assistance was provided by Proper Medical Writing Sp. z o.o., Warsaw, Poland.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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  1. ENT Department, Children’s Hospital, 4/24 Niekłańska Str., 03-924, Warsaw, Poland

    Beata Zielnik-Jurkiewicz

  2. Department of Microwave Safety, Military Institute of Hygiene and Epidemiology, 4 Kozielska Str., 01-163, Warsaw, Poland

    Wanda Stankiewicz-Szymczak

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Correspondence to Beata Zielnik-Jurkiewicz.

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Zielnik-Jurkiewicz, B., Stankiewicz-Szymczak, W. Pro-inflammatory interleukins in middle ear effusions from atopic and non-atopic children with chronic otitis media with effusion. Eur Arch Otorhinolaryngol 273, 1369–1378 (2016). https://doi.org/10.1007/s00405-015-3683-9

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