TNF-α and TGF-β Contributes in Recurrent Otorrhea of Active Mucosal Chronic Otitis Media

Dewi Pratiwi, Marisa Rizqiana, Adisetya Wicaksono, Defitaria Permatasari, Ratna Dwi Restuti, Tri Nugraha Susilawati, Sutarno Sutarno


BACKGROUND: Active mucosal chronic otitis media (COM) is prevalent in lower-income countries and is associated with recurrent episodes of otorrhea due to chronic inflammation of the middle ear. Cytokines, which are well-known for their effects on the immune system, play an important role in the inflammatory response and tissue remodeling. The specific contributions of proinflammatory and immunoregulatory cytokines in the pathophysiology of active mucosal COM remain unclear. This study aimed to compare the levels of serum tumor necrosis factor (TNF)-α and transforming growth factor (TGF)-β in patients with active mucosal COM vs. healthy subjects.

METHODS: Total 20 subjects with active mucosal COM and 20 healthy subjects participated in this study. The levels of serum TNF-α and TGF-β were measured using enzyme-linked immunosorbent assay (ELISA).

RESULTS: The average level of serum TNF-α in subjects with active mucosal COM was significantly higher compare to the healthy subjects (46.373±41.76 pg/mL vs. 15.021±7.16 pg/mL; p=0.004). In contrast, the average level of serum TGF-β in subjects with active mucosal COM was lower compared to the healthy subjects, although the difference is not statistically significant (9.963±3.2 ng/mL vs. 11.78±8.48 ng/mL; p=0.552). Further analysis showed that in subjects with active mucosal COM, the levels of serum TNF-α had a medium positive correlation with the level of TGF-β (r=0.525; p=0.018).

CONCLUSION: TNF-α and TGF-β, which are proinflammatory and immunoregulatory cytokines, may contribute to the pathogenesis of recurrent episodes of otorrhea in an active mucosal COM.

KEYWORDS: tumor necrosis factor-α, transforming growth factor-β, active mucosal chronic otitis media

Full Text:



Orji F. A survey of the burden of management of chronic suppurative otitis media in a developing Country. Ann Med Health Sci Res. 2013; 3(4): 598–601, CrossRef.

Li MG, Hotez PJ, Vrabec JT, Donovan DT. Is Chronic Suppurative Otitis Media a Neglected Tropical Disease? PLoS Negl Trop Dis. 2015; 9(3): e0003485, CrossRef.

World Health Organization. Chronic Suppurative Otitis Media: Burden of Illness and Management Options. Geneva: World Health Organization; 2004, article.

Muftah S, Mackenzie I, Faragher B, Brabin B. Prevalence of chronic suppurative otitis media (CSOM) and associated hearing impairment among school-aged children in Yemen. Oman Med J. 2015; 30(5): 358–65, CrossRef.

Mittal R, Lisi CV, Gerring R, Mittal J, Mathee K, Narasimhan G, et al. Current concepts in the pathogenesis and treatment of chronic suppurative otitis media. J Med Microbiol. 2015; 64(10): 1103–16, CrossRef.

Massa HM, Lim DJ, Kurono Y, Cripps AW. Middle ear and eustachian tube mucosal immunology. Mucosal Immunol Fourth Ed. 2015; 2(2): 1923–42, CrossRef.

Kany S, Vollrath JT, Relja B. Cytokines in inflammatory disease. Int J Mol Sci. 2019; 20(23): 6008, CrossRef.

Kuczkowski J, Sakowicz-Burkiewicz M, Iycka-Świeszewska E, Mikaszewski B, Pawełczyk T. Expression of tumor necrosis factor-α, interleukin-1α, interleukin-6 and interleukin-10 in chronic otitis media with bone osteolysis. ORL J Otorhinolaryngol Relat Spec. 2011; 73(2): 93–9, CrossRef.

Si Y, Zhang ZG, Chen SJ, Zheng YQ, Chen Y Bin, Liu Y, et al. Attenuated TLRs in middle ear mucosa contributes to susceptibility of chronic suppurative otitis media. Hum Immunol. 2014; 75(8): 771–6, CrossRef.

Schilder AGM, Chonmaitree T, Cripps AW, Rosenfeld RM, Casselbrant ML, Haggard MP, et al. Otitis media. Nat Rev Dis Primer. 2016; 2(1): 16063, CrossRef.

Sulaeman A, Amiruddin AR, Lawrence GS. Metabolic syndrome (MetS) and nonalcoholic steatohepatitis (NASH): study of biochemical markers free fatty acid (FFA), total antioxidant status (TAOS), adiponectin, transforming growth factor (TGF-beta1), in occurence of NASH. Indones Biomed J. 2009; 1(1): 40–4, CrossRef.

Qiu J, Wang Y, Guo W, Xu L, Mou Y, Cui L, et al. Role of TGF‑β1‑mediated epithelial‑mesenchymal transition in the pathogenesis of tympanosclerosis. Exp Ther Med. 2020; 20(6): 1–1, CrossRef.

Wang B, Cheng Y, Xu M. Characterization of the t-cell subpopulations in the granulation tissues of chronic suppurative otitis media. Biomed Rep. 2016; 4(6): 694–8, CrossRef.

Gleeson M, Browning GG, Burton MJ, Clarke R, John H, Jones NS, et al. Scott-Brown’s Otorhinolaryngology Head and Neck Surgery. 7th ed. London: Hodder Arnold; 2008, CrossRef.

Ibekwe TS, Nwaorgu OGB. Classification and management challenges of otitis media in a resource-poor country. Niger J Clin Pract. 2011; 14(3): 262–9, CrossRef.

Abraham ZS, Ntunaguzi D, Kahinga AA, Mapondella KB, Massawe ER, Nkuwi EJ, et al. Prevalence and etiological agents for chronic suppurative otitis media in a tertiary hospital in Tanzania. BMC Res Notes. 2019; 12(1): 429, CrossRef.

Metri Basavaraj C, Jyothi P. Chronic suppurative otitis media (CSOM): Etiological agents and antibiotic sensitivity pattern of the isolates. J Med Bangladesh. 2015; 16(2): 78–82, CrossRef.

Poluan FH, Utomo BSR, Dharmayanti J. Profile benign type of chronic suppurative otitis media in general hospital of the christian university of Indonesia. Int J Res Granthaalayah. 2021; 9(4): 229–39, CrossRef.

Al-Sadeeq H, Algarni Z, Alobaid A, Aloyaid A, Alotaibi M, Al-Qwizani A, et al. Otitis media among elderly: incidence, complication and prevention. Int J Community Med Public Health. 2018; 5(3): 839–41, CrossRef.

Aarhus L, Tambs K, Kvestad E, Engdahl B. Childhood otitis media: a cohort study with 30-year follow-up of hearing (The HUNT Study). Ear Hear. 2015; 36(3): 302–8, CrossRef.

Islam MR, Abdullah M, Kabir AL, Islam SS, Rashid MHO. Hearing loss in chronic suppurative otitis media (CSOM). Bangladesh J Otorhinolaryngol. 2020; 23(1): 59–66, CrossRef.

Hiremath B, Mudhol RS, Vagrali MA. Bacteriological profile and antimicrobial susceptibility pattern in chronic suppurative otitis media: a 1-year cross-sectional study. Indian J Otolaryngol Head Neck Surg. 2019; 71(S2): 1221–6, CrossRef.

Wahyono DJ, Darmawan AB, Alfason L, Simbolon R, Wijayanti SPM, Paramaiswari WT, et al. Staphylococcus aureus and pseudomonas aeruginosa in tubotympanic chronic suppurative otitis media patients in Purwokerto, Indonesia. Indones Biomed J. 2020; 12(4): 340–8, CrossRef.

Xu J, Du Q, Shu Y, Ji J, Dai C. Bacteriological profile of chronic suppurative otitis media and antibiotic susceptibility in a tertiary care hospital in Shanghai, China. Ear Nose Throat J. 2021; 100(9): NP391–6, CrossRef.

Juyal D, Negi V, Sharma M, Adekhandi S, Prakash R, Sharma N. Significance of fungal flora in chronic suppurative otitis media. Ann Trop Med Public Health. 2014; 7(2): 120–3, CrossRef.

Chirwa M, Mulwafu W, Aswani J, Masinde P, Mkakosya R, Soko D. Microbiology of chronic suppurative otitis media at Queen Elizabeth Central Hospital, Blantyre, Malawi: A cross-sectional descriptive study. Malawi Med J. 1970; 27(4): 120–4, CrossRef.

Chandra Sahu M, Swain SK. Surveillance of antibiotic sensitivity pattern in chronic suppurative otitis media of an Indian teaching hospital. World J Otorhinolaryngol - Head Neck Surg. 2019; 5(2): 88–94, CrossRef.

Khatun MstR, Alam KhMdF, Naznin M, Salam MdA. Microbiology of chronic suppurative otitis media: an update from a tertiary care hospital in Bangladesh. Pak J Med Sci. 2021; 37(3): 821–6, CrossRef.

Kaur R, Casey J, Pichichero M. Cytokine, chemokine, and toll-like receptor expression in middle ear fluids of children with acute otitis media: innate immune response in children with AOM.Laryngoscope. 2015; 125(1): E39–44, CrossRef.

Lee HY, Chung JH, Lee SK, Byun JY, Kim Y Il, Yeo SG. Toll-like receptors, cytokines & nitric oxide synthase in patients with otitis media with effusion. Indian J Med Res. 2013; 138(4): 523–30, PMID.

Rout MR, Mohanty D, Vijaylaxmi Y, Kamalesh B, Chakradhar M. Prevalence of cholesteatoma in chronic suppurative otitis media with central perforation. Indian J Otol. 2012; 18(1): 7–10, CrossRef.

Tateossian H, Morse S, Simon MM, Dean CH, Brown SDM. Interactions between the otitis media gene, Fbxo11, And p53 in the mouse embryonic lung. DMM Dis Models Mech. 2015; 8(12): 1531–42, CrossRef.

Bhutta MF, Thornton RB, Kirkham LAS, Kerschner JE, Cheeseman MT. Understanding the aetiology and resolution of chronic otitis media from animal and human studies. DMM Dis Models Mech. 2017; 10(11):1 289–300, CrossRef.

Lee SU, Kim MO, Kang MJ, Oh ES, Ro H, Lee RW, et al. Transforming growth factor β inhibits muc5ac expression by smad3/hdac2 complex formation and nf-κb deacetylation at k310 in nci-h292 cells. Mol Cells. 2021; 44(1): 38–49, CrossRef.


Indexed by:





The Prodia Education and Research Institute