Eosinophil chemoattractants in the middle ear of patients with eosinophilic otitis media.
BACKGROUND
Patients with intractable otitis media associated with bronchial asthma have an extensive accumulation of eosinophils in the effusion and mucosa of the middle ear; this condition is called eosinophilic otitis media (EOM). It remained to be determined how eosinophils accumulate in the middle ear.


OBJECTIVE
To clarify the pathogenesis of middle ear diseases, we measured the concentration of eosinophil chemoattractants in middle ear effusion (MEE), and carried out immunohistochemical studies of middle ear mucosa specimens to demonstrate the expression of eosinophil chemoattractants.


METHODS
Middle ear effusion samples were obtained from 15 EOM patients with bronchial asthma and from six controls for the measurement of eosinophil cationic protein (ECP), IL-5, eotaxin and regulated on activation, normal T expressed and secreted concentrations. Middle ear mucosa samples were also taken from 14 EOM patients and 16 controls for immunohistochemical study. In 10 EOM patients, the numbers of immunoreactive cells as well as apoptotic cells were determined before and after the topical application of triamcinolone acetonide into the middle ear.


RESULTS
In EOM, significantly higher ECP and IL-5 concentrations were detected in MEE than in serum, and ECP, IL-5 and eotaxin concentrations in MEE were higher in the EOM patients than in the controls. ECP concentration positively correlated with that of IL-5. Immunohistochemically, the numbers of cells positive for EG2 and ecalectin were significantly higher in the EOM patients than in the controls. After the topical application of triamcinolone acetonide, the numbers of infiltrating cells and immunoreactive cells distinctly decreased, whereas the number of apoptotic cells significantly increased.


CONCLUSIONS
In EOM, locally produced IL-5 may play a crucial role in the accumulation of eosinophils in the middle ear. Chemokines such as ecalectin and eotaxin are also produced in the middle ear, and help activate and enhance the survival of eosinophils to induce the intractable condition in the middle ear. The topical application of triamcinolone acetonide induces the apoptosis of not only eosinophils but also eosinophil chemoattractant-producing cells, thereby improving the middle ear condition.
Iino
Y
Y
Department of Otolaryngology, Teikyo University School of Medicine, Tokyo, Japan. yiorl@med.teikyo-u.ac.jp
Kakizaki
K
K
Katano
H
H
Saigusa
H
H
Kanegasaki
S
S
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000187:drug effects; D001249:Asthma / Q000150:complications / Q000378:metabolism; D054413:Chemokine CCL11; D018946:Chemokine CCL5 / Q000096:biosynthesis / Q000235:genetics; D019742:Chemokines, CC / Q000096:biosynthesis / Q000235:genetics; D002630:Chemotactic Factors / Q000032:analysis*; D002634:Chemotaxis, Leukocyte; D004432:Ear, Middle / Q000737:chemistry* / Q000473:pathology; D047150:Eosinophil Cationic Protein / Q000032:analysis; D004802:Eosinophilia / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D005260:Female; D037161:Galectins / Q000096:biosynthesis / Q000235:genetics; D015870:Gene Expression; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D015848:Interleukin-5 / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000737:chemistry / Q000473:pathology; D010034:Otitis Media with Effusion / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D014222:Triamcinolone Acetonide / Q000627:therapeutic use
C515456:CCL11 protein, human; D054413:Chemokine CCL11; D018946:Chemokine CCL5; D019742:Chemokines, CC; D002630:Chemotactic Factors; D037161:Galectins; D005938:Glucocorticoids; D015848:Interleukin-5; C105032:LGALS9 protein, human; D012333:RNA, Messenger; D047150:Eosinophil Cationic Protein; C479220:RNASE3 protein, human; D014222:Triamcinolone Acetonide