Detection and localization of interleukin-6 in the rat middle ear during experimental acute otitis media, using mRNA in situ hybridization and immunohistochemistry

Objective: Otitis media is one of the most common diseases among children. A well-known sequela of acute, chronic, and secretory otitis media is tympa nosclerosis. With the exception of surgery, there is no causal treatment av ailable for this condition, which may cause hearing disabilities. This stud y aimed to describe the localization of interleukin (IL)-6 mRNA and its gen eproduct in the rat middle ear during pneumococcal otitis media. IL-6 is kn own to be involved in inflammatory and boneremodeling processes. Methods: U sing an experimental model of pneumococcal acute otitis media, the expressi on of interleukin IL-6, was analyzed. Sprague-Dawley rats were sacrificed a t different time points varying from 1 h to 6 days intervals after inoculat ion. The middle ears were analyzed by messenger RNA in situ hybridization, and by immunohistochemistry with cell-type specific antibodies directed aga inst IL-6. Results: Transcripts of IL-6 were observed only on day 1 post-in oculation, whereas the final gene product was observed at all intervals aft er inoculation. IL-6 was localized in the bony part of the bulla nearest to the mucosa, around mucosal vessels, and in the ciliae of the mucosal epith elium. The results demonstrated that IL-6 was synthesized locally as early as 1 h after bacterial middle ear challenge, and that although transcriptio n could not be detected after 24 h, the cytokine product persisted for at l east 5 days after the infection was introduced. Conclusions. IL-6 was shown to be produced early in the inflammatory process during induced pneumococc al otitis media in the rat. No production was seen after 24 h although the protein remained in the tissue for at least 5 days. IL-6 could initiate a d ifferentiation of macrophages to osteoclasts and thereby participate in a b oneremodeling process leading to tympanosclerosis development. (C) 2001 Pub lished by Elsevier Science Ireland Ltd.