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Middle ear fluid cytokine and inflammatory cell kinetics in the chinchilla otitis media model
K Sato1, C L Liebeler, M K Quartey
1Otitis Media Research Center, University of Minnesota, Minneapolis, Minnesota, USA.
Abstract:
Streptococcus pneumoniae is the most frequent microbe causing middle ear infection. The pathophysiology of pneumococcal otitis media has been characterized by measurement of local inflammatory mediators such as inflammatory cells, lysozyme, oxidative metabolic products, and inflammatory cytokines. The role of cytokines in bacterial infection has been elucidated with animal models, and interleukin (IL)-1beta, IL-6, and IL-8 and tumor necrosis factor alpha (TNF-alpha) are recognized as being important local mediators in acute inflammation. We characterized middle ear inflammatory responses in the chinchilla otitis media model after injecting a very small number of viable pneumococci into the middle ear, similar to the natural course of infection. Middle ear fluid (MEF) concentrations of IL-1beta, IL-6, IL-8, and TNF-alpha were measured by using anti-human cytokine enzyme-linked immunosorbent assay reagents. IL-1beta showed the earliest peak, at 6 h after inoculation, whereas IL-6, IL-8, and TNF-alpha concentrations were increasing 72 h after pneumococcal inoculation. IL-6, IL-8, and TNF-alpha but not IL-1beta concentrations correlated significantly with total inflammatory cell numbers in MEF, and all four cytokines correlated significantly with MEF neutrophil concentration. Several intercytokine correlations were significant. Cytokines, therefore, participate in the early middle ear inflammatory response to S. pneumoniae.
Insights
This study shows that key inflammatory cytokines, including interleukin (IL)-1beta, IL-6, IL-8, and tumor necrosis factor alpha (TNF-alpha), play a significant role in the early stages of middle ear infections caused by Streptococcus pneumoniae.
Area of Science:
- Otolaryngology
- Immunology
- Microbiology
Background:
- Streptococcus pneumoniae is a primary cause of middle ear infections (otitis media).
- Inflammatory mediators, including cytokines, are crucial in the pathophysiology of bacterial infections.
- Previous research has identified specific cytokines involved in acute inflammation.
Purpose of the Study:
- To characterize middle ear inflammatory responses to Streptococcus pneumoniae in a chinchilla model.
- To measure concentrations of key cytokines in middle ear fluid (MEF) following pneumococcal inoculation.
- To correlate cytokine levels with inflammatory cell presence and concentration.
Main Methods:
- Utilized a chinchilla otitis media model by inoculating a small number of viable Streptococcus pneumoniae.
- Measured concentrations of interleukin (IL)-1beta, IL-6, IL-8, and tumor necrosis factor alpha (TNF-alpha) in middle ear fluid (MEF).
- Employed anti-human cytokine enzyme-linked immunosorbent assay (ELISA) reagents for cytokine measurement.
Main Results:
- Interleukin (IL)-1beta peaked earliest (6 hours post-inoculation).
- IL-6, IL-8, and TNF-alpha concentrations increased up to 72 hours post-inoculation.
- IL-6, IL-8, and TNF-alpha correlated with total inflammatory cells and neutrophils in MEF; all four cytokines correlated with neutrophil concentration.
Conclusions:
- Cytokines are integral participants in the early inflammatory response within the middle ear during Streptococcus pneumoniae infections.
- Specific cytokine profiles and their correlations with inflammatory cells provide insights into otitis media pathogenesis.
- The study highlights the dynamic role of cytokines in mediating the host's response to pneumococcal middle ear infection.