Murine model of interleukin-8-induced otitis media.
Interleukin-8 (IL-8), a potent inflammatory mediator that is thought to control leukocyte recruitment and activation during inflammatory reactions, has been implicated in a variety of inflammatory diseases. Recent studies in our laboratory have demonstrated the presence of IL-8 in chronically inflamed human middle ear effusions. These data have led us to hypothesize that IL-8 is responsible for the leukocyte recruitment 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 directly induce inflammation in the murine middle ear. For these studies, ICR mice were used to test the hypothesis that IL-8 could directly induce inflammation in the middle ear. Murine middle ears received 8-mL transtympanic injections of human IL-8 (25 mg/mL) in saline, heat-killed Streptococcus pneumoniae (1 x 10(8)/mL), or normal saline. Temporal bones were removed at 1, 4, 8, 24, and 48 hours, decalcified, and processed for histologic examination. Noninjected murine temporal bones served 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 infiltration in the SES peaking at 4 to 8 hours and resolving by 48 hours. Bacteria-injected ears demonstrated findings similar to, although not as extensive as, those found in IL-8-injected ears (i.e., inflammatory reactions 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 and support the concept that IL-8 may be one of the key cytokines responsible for the leukocyte accumulation and activation seen in otitis media.
Johnson
M
M
Surgical Research Center, Department of Surgery, University of Connecticut School of Medicine, Farmington 06030-3105, U.S.A.
Leonard
G
G
Kreutzer
D L
DL
D000818:Animals; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000494:pharmacology* / Q000502:physiology; D008213:Lymphocyte Activation; D051379:Mice; D008813:Mice, Inbred ICR; D009504:Neutrophils / Q000276:immunology; D010033:Otitis Media / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D011008:Pneumococcal Infections / Q000276:immunology / Q000473:pathology; D013701:Temporal Bone / Q000473:pathology
D016209:Interleukin-8