Interleukin-1 receptor antagonist as an adjunct in the treatment of Haemophilus influenzae otitis media in the chinchilla.

Objectives This purpose of this study was to investigate the effect of blockade of the inflammatory cytokine pathway on experimentally induced otitis media in the chinchilla model. Study Design Pilot, randomized placebo-controlled trial. Methods Ampicillin-sensitive Haemophilus influenzae otitis media was induced in 45 adult chinchillas. The animals were randomly assigned to the following treatment groups: 1) transbullar injections (TBI) of interleukin-1 receptor antagonist (IL-1ra) and intramuscular ampicillin, 2) TBI of saline and intramuscular ampicillin, 3) TBI of IL-1ra and intramuscular saline or 4) TBI of saline and intramuscular saline. Blinded investigators measured resolution of otitis media by otomicroscopy, tympanogram, and culture results. Results Comparisons were made between the treatment groups to assess the ability of IL-1ra to assist with resolution of otitis media using exact two-group binomial tests with the StatXact statistical program. The group with TBI of IL-1ra and intramuscular ampicillin as a treatment demonstrated trends suggesting more rapid resolution of positive cultures and more rapid and complete return to normal results on tympanograms and otomicroscopic findings compared with the group treated with TBI of saline and intramuscular ampicillin. These trends did not achieve statistical significance with the relatively small sample sizes used in this pilot study. Conclusions This investigation provides further evidence that the inflammatory cytokine cascade plays a significant role in the pathophysiology of otitis media and that modulation of this inflammatory pathway may provide novel and efficacious treatments for otitis media. Further studies with larger groups of animals are warranted to determine whether the trends identified in this pilot study are reproducible and achieve statistical significance.