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Eicosanoid synthesis and inactivation in healthy and infected chinchilla middle ears
J D Swarts1, J Y Westcott, K H Chan
1Department of Otolaryngology, University of Colorado, Health Sciences Center Denver, USA.
Abstract:
Otitis media (OM) is an inflammatory reaction of the middle ear (ME) elicited by a variety of stimuli including tubal obstruction, allergy and bacterial infection. The leukotrienes and prostaglandins are among the earliest mediators produced in response to these insults. Their measured levels in human and animal models span a broad range of concentrations. However, their baseline levels and metabolic fates are unknown for the ME. Their dynamics in the ME were examined using the chinchilla animal model, tritiated eicosanoids and a lavage procedure. Prostaglandin levels in the normal ME were 10 times higher than the 34 pg/ear observed for the leukotrienes and thromboxane B2. These levels were significantly increased by the calcium ionophore A23187 and bacterial infection. Leukotrience C4 was the most and prostaglandin E2 the least persistent eicosanoid in the ME. Their residence time in the ME was increased by infection. The rank order of eicosanoid concentrations among comparable studies was surprisingly constant, with prostaglandin E2 the most abundant and the leukotrienes the least. Comparisons of eicosanoid levels from A23187 stimulation and the infectious models sampled at 3 days suggest that the higher levels observed in the infectious models may represent basal eicosanoid production for hyperplastic ME mucosa.
Insights
This study investigated eicosanoid dynamics in the middle ear (ME), finding prostaglandin levels significantly higher than leukotrienes in normal conditions. Bacterial infection increased these levels, suggesting a role in otitis media pathogenesis.
Area of Science:
- Biochemistry
- Otolaryngology
- Inflammation Research
Background:
- Otitis media (OM) involves middle ear inflammation triggered by various factors.
- Eicosanoids like leukotrienes and prostaglandins are early inflammatory mediators.
- Baseline levels and metabolic fates of eicosanoids in the middle ear are largely unknown.
Purpose of the Study:
- To examine the dynamics of eicosanoids in the middle ear.
- To quantify baseline and stimulated eicosanoid levels in a relevant animal model.
- To understand the impact of infection on eicosanoid persistence.
Main Methods:
- Utilized the chinchilla animal model.
- Employed tritiated eicosanoids for tracking.
- Performed middle ear lavage to collect samples.
- Stimulated with calcium ionophore A23187 and induced bacterial infection.
Main Results:
- Normal middle ear prostaglandin levels were 10x higher than leukotrienes and thromboxane B2.
- Levels of these mediators significantly increased following A23187 stimulation and bacterial infection.
- Leukotriene C4 exhibited the longest persistence, while prostaglandin E2 was the least persistent.
- Infection prolonged the residence time of eicosanoids in the middle ear.
- Infectious models showed higher eicosanoid levels, potentially reflecting basal production in hyperplastic middle ear mucosa.
Conclusions:
- Eicosanoid levels and dynamics in the middle ear are significantly influenced by stimuli and infection.
- Prostaglandins are more abundant, while leukotrienes are more persistent in the middle ear.
- Findings suggest a role for eicosanoids in the inflammatory processes of otitis media.