Infection and Immunity, July 2000, p. 4024-4031, Vol. 68, No. 7
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Department of Surgery/Otolaryngology, University of California at San Diego School of Medicine and Veterans Affairs Medical Center, La Jolla, California
Received 21 December 1999/Returned for modification 29 February 2000/Accepted 4 April 2000
Acute otitis media (AOM) elicits potent inflammatory responses from
the cells of the middle ear mucosa as well as from infiltrating leukocytes. To explore host responses during experimental AOM induced
by Streptococcus pneumoniae type 3 and nontypeable
Haemophilus influenzae (NTHi), otomicroscopy findings and
expression of cytokine genes in the middle ear were monitored up to 1 month postinoculation. The mucosa and infiltrating cells responded
rapidly to the bacterial challenge. Otomicroscopically, AOM appeared 1 day after NTHi inoculation and 3 days after pneumococcus inoculation.
Pneumococcal AOM was more severe than NTHi otitis, but in general,
lower transcript levels were detected in pneumococcus-infected than in
NTHi-infected animals. Interleukin-6 (IL-6) mRNA levels peaked at 3 to
6 h for both pneumococcus-infected and NTHi-infected animals.
IL-1
, tumor necrosis factor alpha, and IL-10 mRNA levels peaked at
6 h for NTHi otitis and 1 to 3 days for pneumococcal otitis.
Comparing otomicroscopy with expression profiles, it would appear that
the majority of cytokine mRNAs had passed their peak before the AOM diagnosis could be made clinically. Only transforming growth factor
mRNA followed a slower time course, peaking very late and continuing expression even after the AOM was otomicroscopically resolved. IL-2 and
IL-4 mRNAs were not detected in any animal at any time. Most of the
investigated cytokines are very early markers for AOM and may be
involved in initiation of inflammation, but they would be poor targets
for pharmacological manipulation since their levels decline before
clinical signs appear.
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