MURINE MODEL OF INTERLEUKIN-8-INDUCED OTITIS-MEDIA

Interleukin-8 (IL-8), a potent inflammatory mediator that is thought t o control leukocyte recruitment and activation during inflammatory rea ctions, has been implicated in a variety of inflammatory diseases. Rec ent studies in our laboratory have demonstrated the presence of IL-8 i n chronically inflamed human middle ear effusions. These data have led us to hypothesize that IL-8 is responsible for the leukocyte recruitm ent seen in otitis media. Because the effect of IL-8 on the middle ear mucosa has not been investigated and therefore its role in middle ear inflammation is not known, we investigated the ability of IL-8 to dir ectly induce inflammation in the murine middle ear. For these studies, ICR mice were used to test the hypothesis that IL-8 could directly in duce inflammation in the middle ear. Murine middle ears received 8-mL transtympanic injections of human IL-8 (25 mg/mL) in saline, heat-kill ed Streptococcus pneumoniae (1 x 10(8)/mL), or normal saline. Temporal bones were removed at 1, 4, 8, 24, and 48 hours, decalcified, and pro cessed for histologic examination. Noninjected murine temporal bones s erved as controls. Normal saline-injected ears demonstrated little to no change as compared with temporal bones from noninjected ears. IL-8- injected ears histologically demonstrated thickening of the epithelial layer and subepithelial space (SES), with inflammatory cell infiltrat ion in the SES peaking at 4 to 8 hours and resolving by 48 hours. Bact eria-injected ears demonstrated findings similar to, although not as e xtensive as, those found in IL-8-injected ears (i.e., inflammatory rea ctions peaked at 8 to 24 hours and resolved by 72 hours). Our results demonstrate that IL-8 is a potent inducer of middle ear inflammation a nd support the concept that IL-8 may be one of the key cytokines respo nsible for the leukocyte accumulation and activation seen in otitis me dia.