Inflammation in the Middle Ear of Children With Recurrent or Chronic Otitis Media Is Associated With Bacterial Load

Stol, Kim; Diavatopoulos, Dimitri A.; Graamans, K.; Engel, Joost A.M.; Melchers, Willem J. G.; Savelkoul, H.F.J.; Hays, John P.; Warris, Adilia; Hermans, Peter W. M.

doi:10.1097/inf.0b013e3182611d6b

Cited by 19 publications

(14 citation statements)

References 39 publications

(36 reference statements)

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“…However, we can conclude that if respiratory viruses were present in MEF, they induce low proinflammatory responses. Consistent with our conclusion, Stol et al showed no association of viruses and changes in cytokine levels in chronic OM …”

Section: Discussionsupporting

confidence: 93%

Cytokine, chemokine, and toll‐like receptor expression in middle ear fluids of children with acute otitis media

2014

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Objective: Acute Otitis Media (AOM) is a common bacterial infection in childhood that causes an inflammatory response in the middle ear. Leukocytes produce different inflammatory molecules in-vitro when stimulated with Gram-positive and Gram-negative bacteria. The major causes of AOM are Streptococcus pneumoniae, Nontypeable Haemophilus influenzae andMoraxella catarrhalis. We sought to assess differences in cytokines, chemokines and expression of Toll-like receptors (TLRs) at onset of AOM based on bacterial culture results. Study Design: Middle ear fluids (MEF) from 66 children with AOM were studied. Methods: Innate immune genes, cytokines (IL-6, IL-8, IL-10, IL1-β, TNF-α), chemokines (CCL2, CCL3, CCL4, CCR5, CXCR3) and Toll-like receptor (TLR2, TLR4 & TLR9) expression was measured using real-time RT-PCR from MEF collected in-vivo by tympanocentesis. Results: Culture positive MEFs had higher levels of all cytokines and chemokines (9-300 folds) as compared to MEFs that were culture negative. PCR positive/culture negative MEF for otopathogens showed significant differences (p<0.01) in TLR2, TLR4 and TLR9 expression (6-31 fold), but cytokine and chemokine levels were similar compared to PCR negative/culture negative MEF. No significant differences were found in the cytokine/chemokine/TLR levels among the bacterial otopathogen species. However, higher levels of TLRs, and all the cytokine and chemokines were detected when more than one bacterial species was present compared to single otopathogens. Conclusion: Expression levels of pro-inflammatory cytokines/chemokines and TLRs are elevated in AOM children with a bacterial otopathogen, and are dependent on the number of bacterial species identified. Level of Evidence: NA

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Section: Discussionsupporting

confidence: 93%

Cytokine, chemokine, and toll‐like receptor expression in middle ear fluids of children with acute otitis media

2014

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“…Elevation of IL-8 level is a marker for ongoing inflammation, which can be induced by bacterial infection and other injuries in the middle ear. 40 Our study showed that both bacterial infection and the presence of pepsin A were correlated with elevated IL-8 level in the middle ear. Studies in vitro have shown that exposure to cytokines such as IL-8 in human middle ear epithelium can up-regulate mucin expression.…”

Section: Discussionsupporting

confidence: 49%

“…40 Similarly, in animal studies, directly injecting a very small number of viable pneumococci into the middle ear resulted in elevated levels of IL-6, IL-8, and TNF in the middle ears. 40,45 As expected, we also found a strong correlation between bacterial infection and all 3 inflammatory cytokines, confirming the role played by bacterial infection on the level of inflammation in the ears and its independent contribution to middle ear inflammation (data not shown). However, positive pepsin or increased pepsin A levels did not show as strong an association with infection as we had initially hypothesized.…”

Section: Discussionmentioning

confidence: 97%

The Role of Gastric Pepsin in the Inflammatory Cascade of Pediatric Otitis Media

O’Reilly

Soundar

Tonb

et al. 2015

JAMA Otolaryngol Head Neck Surg

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“…Viral replication induced epithelial and mucosal degradation, and the ensuing innate immune response yield diminished capacity to avert secondary bacterial infections. Recent clinical and experimental data suggest that influenza virus infection may exert its influence beginning in the URT by enhancing susceptibility to bacterial colonization (14, 47, 48) and increasing NP carriage density (36). …”

Section: Discussionmentioning

confidence: 99%

Live Attenuated Influenza Vaccine Enhances Colonization of Streptococcus pneumoniae and Staphylococcus aureus in Mice

Mina

McCullers

Klugman

2014

mBio

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Community interactions at mucosal surfaces between viruses, like influenza virus, and respiratory bacterial pathogens are important contributors toward pathogenesis of bacterial disease. What has not been considered is the natural extension of these interactions to live attenuated immunizations, and in particular, live attenuated influenza vaccines (LAIVs). Using a mouse-adapted LAIV against influenza A (H3N2) virus carrying the same mutations as the human FluMist vaccine, we find that LAIV vaccination reverses normal bacterial clearance from the nasopharynx and significantly increases bacterial carriage densities of the clinically important bacterial pathogens Streptococcus pneumoniae (serotypes 19F and 7F) and Staphylococcus aureus (strains Newman and Wright) within the upper respiratory tract of mice. Vaccination with LAIV also resulted in 2- to 5-fold increases in mean durations of bacterial carriage. Furthermore, we show that the increases in carriage density and duration were nearly identical in all aspects to changes in bacterial colonizing dynamics following infection with wild-type (WT) influenza virus. Importantly, LAIV, unlike WT influenza viruses, had no effect on severe bacterial disease or mortality within the lower respiratory tract. Our findings are, to the best of our knowledge, the first to demonstrate that vaccination with a live attenuated viral vaccine can directly modulate colonizing dynamics of important and unrelated human bacterial pathogens, and does so in a manner highly analogous to that seen following wild-type virus infection.

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Inflammation in the Middle Ear of Children With Recurrent or Chronic Otitis Media Is Associated With Bacterial Load

Abstract: The presence of bacteria, but not viruses, is associated with an increased inflammatory response in the middle ear of children with recurrent or chronic OM.

Cited by 19 publications

References 39 publications

Cytokine, chemokine, and toll‐like receptor expression in middle ear fluids of children with acute otitis media

Cytokine, chemokine, and toll‐like receptor expression in middle ear fluids of children with acute otitis media

The Role of Gastric Pepsin in the Inflammatory Cascade of Pediatric Otitis Media

Live Attenuated Influenza Vaccine Enhances Colonization of Streptococcus pneumoniae and Staphylococcus aureus in Mice

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