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Neutralizing antibody against granulocyte/macrophage colony–stimulating factor inhibits inflammatory response in experimental otitis media
Author(s) -
Kariya Shin,
Okano Mitsuhiro,
Higaki Takaya,
Makihara Seiichiro,
Haruna Takenori,
Eguchi Motoharu,
Nishizaki Kazunori
Publication year - 2013
Publication title -
the laryngoscope
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.181
H-Index - 148
eISSN - 1531-4995
pISSN - 0023-852X
DOI - 10.1002/lary.23795
Subject(s) - medicine , immunology , granulocyte , granulocyte macrophage colony stimulating factor , tumor necrosis factor alpha , lipopolysaccharide , granulocyte macrophage colony stimulating factor receptor , otitis , macrophage , inflammation , neutralizing antibody , cytokine , antibody , macrophage colony stimulating factor , biology , biochemistry , in vitro , surgery
Objectives/Hypothesis Granulocyte/macrophage colony–stimulating factor is important in the pathogenesis of acute and chronic inflammatory disease. We hypothesized that granulocyte/macrophage colony–stimulating factor plays a pivotal role in middle ear inflammation and that neutralization of granulocyte/macrophage colony–stimulating factor would inhibit neutrophil migration into the middle ear and production of inflammatory mediators. Study Design Animal experiment. Methods We used transtympanic administration of lipopolysaccharide, a major component of gram‐negative bacteria, into mice to induce an experimental otitis media. Control mice received injection of phosphate‐buffered saline into the middle ear cavity. Mice were systemically treated with granulocyte/macrophage colony–stimulating factor neutralizing antibody or control immunoglobulin G via intraperitoneal injection 2 hours before transtympanic injection of lipopolysaccharide or phosphate‐buffered saline. Middle ear effusions were collected. Concentrations of interleukin (IL)‐1β, tumor necrosis factor (TNF)‐α, keratinocyte chemoattractant, and macrophage inflammatory protein‐2 in middle ear effusions were measured by enzyme‐linked immunosorbent assay. Histologic examination of the middle ear was also performed. Results Transtympanic injection of lipopolysaccharide upregulated levels of granulocyte/macrophage colony–stimulating factor, IL‐1β, TNF‐α, keratinocyte chemoattractant, and macrophage inflammatory protein‐2 in the middle ear. Concentrations of cytokines and chemokines were significantly decreased in mice injected with granulocyte/macrophage colony–stimulating factor neutralizing antibody. Infiltration of inflammatory cells into the middle ear cavity induced by lipopolysaccharide was also significantly reduced by neutralization of granulocyte/macrophage colony–stimulating factor. Conclusions Systemic injection of granulocyte/macrophage colony–stimulating factor neutralizing antibody inhibits the middle ear inflammation induced by lipopolysaccharide in mice. Our findings suggest that granulocyte/macrophage colony–stimulating factor may offer a novel therapeutic target for the management of intractable otitis media.