Expression of cytokine genes during pneumococcal and nontypeable Haemophilus influenzae acute otitis media in the rat

Acute otitis media (AOM) elicits potent inflammatory responses from the cel ls of the middle ear mucosa as well as from infiltrating leukocytes, To exp lore host responses during experimental AOM induced by Streptococcus pneumo niae type 3 and nontypeable Haemophilus influenzae (NTHi), otomicroscopy fi ndings and expression of cytokine genes in the middle ear were monitored up to 1 month postinoculation. The mucose and infiltrating cells responded ra pidly to the bacterial challenge. Otomicroscopically, AOM appeared 1 day af ter NTHi inoculation and 3 days after pneumococcus inoculation. Pneumococca l AOM was more severe than NTHi otitis, but in general, lower transcript le vels 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-i nfected and NTHi-infected animals. IL-1 alpha, tumor necrosis factor alpha, and IL-10 mRNA levels peaked at 6 h for NTHi otitis and 1 to 3 days for pn eumococcal otitis. Comparing otomicroscopy with expression profiles, it wou ld appear that the majority of cytokine mRNAs had passed their peak before the AOM diagnosis could be made clinically. Only transforming growth factor beta 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 investigat ed cytokines are very early markers for AOM and may be involved in initiati on of inflammation, but they would be poor targets for pharmacological mani pulation since their levels decline before clinical signs appear.