title: Neutralizing antibody against granulocyte/macrophage colony-stimulating factor inhibits inflammatory response in experimental otitis media.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. skariya@cc.okayama-u.ac.jp
authors.forename: Shin
authors.initials: S
authors.lastname: Kariya
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Okano
authors.forename: Takaya
authors.initials: T
authors.lastname: Higaki
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Makihara
authors.forename: Takenori
authors.initials: T
authors.lastname: Haruna
authors.forename: Motoharu
authors.initials: M
authors.lastname: Eguchi
authors.forename: Kazunori
authors.initials: K
authors.lastname: Nishizaki
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology* / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010033:Otitis Media / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism
chemical_list: D057134:Antibodies, Neutralizing; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor