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 journalArticle

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

Fingerprint

Otitis Media
Granulocyte-Macrophage Colony-Stimulating Factor
Neutralizing Antibodies
Middle Ear
Lipopolysaccharides
Chemokine CXCL2
Otitis Media with Effusion
Injections
Chemotactic Factors
Interleukin-1
Keratinocytes
Tumor Necrosis Factor-alpha
Phosphates
Macrophage Colony-Stimulating Factor
Intraperitoneal Injections
Gram-Negative Bacteria
Chemokines
Neutrophils
Chronic Disease
Immunoglobulin G

Keywords

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

ASJC Scopus subject areas

  • Otorhinolaryngology

Cite this

Neutralizing antibody against granulocyte/macrophage colony-stimulating factor inhibits inflammatory response in experimental otitis media. / Kariya, Shin; Okano, Mitsuhiro; Higaki, Takaya; Makihara, Seiichiro; Haruna, Takenori; Eguchi, Motoharu; Nishizaki, Kazunori.

In: Laryngoscope, Vol. 123, No. 6, 06.2013, p. 1514-1518.

Research output: Contribution to journalArticle

@article{5a7092ba56bc446fbe0e37619ecdbe17,
title = "Neutralizing antibody against granulocyte/macrophage colony-stimulating factor inhibits inflammatory response in experimental otitis media",
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.",
keywords = "chemokine, cytokine, endotoxin, Granulocyte/macrophage colony-stimulating factor, lipopolysaccharide, middle ear, otitis",
author = "Shin Kariya and Mitsuhiro Okano and Takaya Higaki and Seiichiro Makihara and Takenori Haruna and Motoharu Eguchi and Kazunori Nishizaki",
year = "2013",
month = "6",
doi = "10.1002/lary.23795",
language = "English",
volume = "123",
pages = "1514--1518",
journal = "Laryngoscope",
issn = "0023-852X",
publisher = "John Wiley and Sons Inc.",
number = "6",

}

TY - JOUR

T1 - Neutralizing antibody against granulocyte/macrophage colony-stimulating factor inhibits inflammatory response in experimental otitis media

AU - Kariya, Shin

AU - Okano, Mitsuhiro

AU - Higaki, Takaya

AU - Makihara, Seiichiro

AU - Haruna, Takenori

AU - Eguchi, Motoharu

AU - Nishizaki, Kazunori

PY - 2013/6

Y1 - 2013/6

N2 - 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.

AB - 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.

KW - chemokine

KW - cytokine

KW - endotoxin

KW - Granulocyte/macrophage colony-stimulating factor

KW - lipopolysaccharide

KW - middle ear

KW - otitis

UR - http://www.scopus.com/inward/record.url?scp=84878154916&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84878154916&partnerID=8YFLogxK

U2 - 10.1002/lary.23795

DO - 10.1002/lary.23795

M3 - Article

C2 - 23172593

AN - SCOPUS:84878154916

VL - 123

SP - 1514

EP - 1518

JO - Laryngoscope

JF - Laryngoscope

SN - 0023-852X

IS - 6

ER -