Cytokine Profiles in a Rat Model of Otitis Media With Effusion Caused by Eustachian Tube Obstruction With and Without Streptococcus pneumoniae Infection

Cytokine expression was studied in a rat model of otitis media with effusion.The left eustachian tube was obstructed (eustachian tube obstruction [ETO]) in 84 rats. Forty-two ears were challenged with, and those rats were treated from day 2 to day 7 with ampicillin. Twelve rats (6 per group) were killed on days 1, 2, 7, 21, 35, 56, and 112; mucosa was harvested and assayed for interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-10 (IL-10), interferon-gamma (IFN-gamma), transforming growth factor-beta (TGF-beta), monocyte chemoattractant protein-1 (MCP-1), and interleukin-8 (IL-8) gene expression, and effusion was assayed for IL-1beta, TNF-alpha, IL-6, IL-10, and macrophage inflammatory protein-2 (MIP-2) protein.Most cytokines were detectable in the effusion from infected ears with ETO on days 1 and 2 only. MIP-2 exhibited a biphasic response. Only effusion MIP-2 was consistently detected in uninfected ears with ETO. Three patterns of mucosal cytokine messenger RNA (mRNA) upregulation were observed: isolated early (IL-1beta, IL-8), isolated late (TNF-alpha, IFN-gamma), and biphasic (MCP-1, IL-6, TGF-beta) responses. Early cytokine mRNA upregulations were observed only in the infected ears with ETO, whereas late upregulations were observed in both groups.Early expression of the assayed cytokines occurred only in ears with active infection. For both groups, a late upregulation of cytokine message but not protein was documented. The profile of cytokine expression during otitis media episodes may be useful in defining etiology, disease stage, and prognosis.