TY - JOUR
T1 - Effect of systemic lipopolysaccharide-induced inflammation on cytokine levels in the murine cochlea
T2 - A pilot study
AU - Quintanilla-Dieck, Lourdes
AU - Larrain, Barbara
AU - Trune, Dennis
AU - Steyger, Peter
N1 - Funding Information:
Funding source: Supported by NIH-NIDCD grants R01 DC004555 (PS), R01 DC005593 (DT), and Department of Otolaryngology at Oregon Health & Science University.
PY - 2013/8
Y1 - 2013/8
N2 - 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.
AB - 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.
KW - aminoglycosides
KW - cochlear cytokines
KW - ototoxicity
KW - sepsis
KW - systemic inflammation
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U2 - 10.1177/0194599813491712
DO - 10.1177/0194599813491712
M3 - Article
C2 - 23736811
AN - SCOPUS:84884194127
SN - 0194-5998
VL - 149
SP - 301
EP - 303
JO - Otolaryngology - Head and Neck Surgery (United States)
JF - Otolaryngology - Head and Neck Surgery (United States)
IS - 2
ER -