High cytokine levels in perforated acute otitis media exudates containing live bacteria

Abstract

Acute otitis media (AOM) is an inflammatory response to microbes in the middle ear, sometimes associated with rupture of the tympanic membrane. Human leukocytes produce different patterns of inflammatory mediators in vitro when stimulated with Gram-positive and Gram-negative bacteria, respectively. Here, we investigated the cytokine and prostaglandin E2 (PGE2) responses in middle ear fluids (MEFs) from children with spontaneously perforated AOM, and related the mediator levels to the presence of pathogens detected by culture (live) or PCR (live or dead). Furthermore, the in vivo cytokine pattern was compared with that induced in leukocytes stimulated by dead bacteria in vitro. MEFs with culturable pathogenic bacteria contained more interleukin (IL)-1β (median: 110 μg/L vs. <7.5 μg/L), tumour necrosis factor (TNF) (6.3 μg/L vs. <2.5 μg/L), IL-8 (410 μg/L vs. 38 μg/L) and IL-10 (0.48 μg/L vs. <0.30 μg/L) than culture-negative fluids, irrespective of PCR findings. IL-6 and PGE2 were equally abundant (69-110 μg/L) in effusions with live, dead or undetectable bacteria. Cytokine levels were unrelated to bacterial species and to the presence or absence of virus. Similar levels of TNF and IL-6 as found in the MEFs were obtained by in vitro stimulation of leukocytes, whereas 11 times more IL-1β and 3.5 times more IL-8 were produced in vivo, and 22 times more IL-10 was produced in vitro. Vigorous production of proinflammatory cytokines accompanies AOM with membrane rupture, regardless of the causative agent, but the production seems to cease rapidly once the bacteria are killed and fragmented. IL-6 and PGE2, however, remain after bacterial disintegration, and may play a role in the resolution phase.

Differences in Innate Immune Response Gene Regulation in the Middle Ear of Children who are Otitis Prone and in those not Otitis Prone

“…The role and requirement for IL-8 in chemotaxis for neutrophil recruitment during recurrent infections have been described in other studies that involved other disease conditions. 30,31 We found fourfold higher levels of SLPI gene expression in children who were sOP. SLPI is generally expressed at mucosal surfaces and plays a role in the defense against the destruction of epithelial tissues by neutrophil elastase.…”

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

“…Although this study focused on children with AOM in which the tympanic membrane ruptured spontaneously, it is important to note that they also found an association between the presence of bacteria and increased levels of cytokines. 27 Thus, both their and our study point to an important role for bacteria in the inflammatory cytokine response during OM. In contrast to the study by Skovsberg et al, we also assessed the impact of bacterial load on the cytokine response.…”

Occult otitis media in dogs with chronic otitis externa – magnetic resonance imaging and association with otoscopic and cytological findings

“…However, the present study found a statistically significant higher risk of OM when rod‐shaped bacteria were present together with inflammatory cells. The presence of inflammatory cells indicates an active immune response, and human studies have shown that an excessive production of proinflammatory cytokines, particularly in the presence of bacteria, can cause damage to the TM . The majority of rod‐shaped bacteria were Pseudomonas spp.…”

“…The presence of inflammatory cells indicates an active immune response, and human studies have shown that an excessive production of proinflammatory cytokines, particularly in the presence of bacteria, can cause damage to the TM. 28,29 The majority of rod-shaped bacteria were Pseudomonas spp. which are known to form biofilms.…”