Neutralizing antibody against granulocyte/macrophage colony-stimulating factor inhibits inflammatory response in experimental otitis media

Shin Kariya, Mitsuhiro Okano, Takaya Higaki, Seiichiro Makihara, Takenori Haruna, Motoharu Eguchi, Kazunori Nishizaki

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1514-1518
Number of pages5
JournalLaryngoscope
Volume123
Issue number6
DOIs
Publication statusPublished - Jun 2013

Keywords

  • Granulocyte/macrophage colony-stimulating factor
  • chemokine
  • cytokine
  • endotoxin
  • lipopolysaccharide
  • middle ear
  • otitis

ASJC Scopus subject areas

  • Otorhinolaryngology

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