Systemic injection of an antibody against granulocyte/macrophage colony-stimulating factor inhibits middle-ear inflammation induced by lipopolysaccharide in mice, study findings show.
Granulocyte/macrophage colony-stimulating factor may therefore offer a novel therapeutic target for the management of intractable otitis media, write Shin Kariya (Okayama University, Kita-ku, Japan) and co-authors.
They induced experimental otitis media in mice by administering lipopolysaccharide, which is a major component of gram-negative bacteria. Lipopolysaccharide has previously been proven to induce otitis media with effusion in experimental models when administered alone into the middle-ear cavity. Control mice received an injection of phosphate-buffered saline into the middle-ear cavity.
Mice were systemically treated with an antibody against granulocyte/macrophage colony-stimulating factor or control immunoglobulin G via intraperitoneal injection 2 hours before a transtympanic injection of lipopolysaccharide or phosphate-buffered saline.
There were 48 mice used in the study, aged 6-12 weeks.
Kariya and team found that transtympanic injection of lipopolysaccharide upregulated levels of granulocyte/macrophage colony-stimulating factor, interleukin-1β, tumor-necrosis factor-α, keratinocyte chemoattractant, and macrophage inflammatory protein-2 in the middle ear at 24 hours.
Moreover, the concentrations of cytokines and chemokines were significantly reduced in mice injected with an antibody against granulocyte/macrophage colony-stimulating factor.
The authors note that the infiltration of inflammatory cells into the middle-ear cavity induced by lipopolysaccharide was also significantly reduced by the neutralization of granulocyte/macrophage colony-stimulating factor.
"The present study showed that treatment with granulocyte/macrophage colony-stimulating factor-neutralizing antibody exerts significant effects on lipopolysaccharide-induced otitis media," say the authors.
"Our findings in this study clearly showed that neutralization of endogenous granulocyte/macrophage colony-stimulating factor by the neutralizing antibody significantly reduced infiltration of inflammatory cells and cytokine production in the middle ear of lipopolysaccharide-challenged mice," they conclude.
The findings are published in The Laryngoscope.
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