title: Effect of systemic lipopolysaccharide-induced inflammation on cytokine levels in the murine cochlea: a pilot study.
abstract: The objective was to detect changes in cytokine expression within cochleae in a murine model of systemic inflammation, with or without aminoglycoside exposure. Four groups of mice received 1 of the following: saline only, systemic bacterial lipopolysaccharides (LPS) for 6 hours to induce endotoxemia and inflammatory responses, systemic gentamicin for 3 hours, or both treatments. After exsanguination, pooled cochleae (4/group) were processed for enzyme-linked immunosorbent assay (ELISA) for 16 cytokines. Gentamicin alone did not change cochlear cytokine levels, while LPS (± gentamicin) substantially elevated cochlear expression of several cytokines, particularly interleukin-1α, interleukin-6, monocyte chemotactic protein-1, macrophage inflammatory protein-1α, and RANTES. Since cytokines increase blood-brain barrier permeability, we hypothesize that cytokine-enhanced permeability of the blood-labyrinth barrier (BLB) could potentiate aminoglycoside-induced ototoxicity. This pilot study demonstrated the feasibility of detecting cytokine expression in murine cochleae using ELISA and facilitates future studies investigating BLB permeability in animal models of systemic inflammation.
authors.affiliation: Department of Otolaryngology Head & Neck Surgery, Oregon Health & Science University, Portland, Oregon 97239-3098, USA. quintani@ohsu.edu
authors.forename: Lourdes
authors.initials: L
authors.lastname: Quintanilla-Dieck
authors.forename: Barbara
authors.initials: B
authors.lastname: Larrain
authors.forename: Dennis
authors.initials: D
authors.lastname: Trune
authors.forename: Peter S
authors.initials: PS
authors.lastname: Steyger
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D003051:Cochlea / Q000378:metabolism* / Q000473:pathology; D015834:Cochlear Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D010865:Pilot Projects
chemical_list: D015415:Biomarkers; D016207:Cytokines; D008070:Lipopolysaccharides
keywords: aminoglycosides; cochlear cytokines; ototoxicity; sepsis; systemic inflammation