Experimental otitis media with effusion induced by leukotriene D4.
OBJECTIVE
inflammatory mediators such as prostaglandins (PGs), leukotrienes (LTs), and platelet-activating factor (PAF) have been identified in human middle ear effusions (MEEs), as well as in the experimentally induced MEEs of animals. However, the exact function of LTs in the middle ear cavity is still unknown. In this study, the role of LTs was investigated using an experimental model in which OME was induced by LTD4.


METHODS
to examine whether leukotrienes (LTs) induce otitis media with effusion (OME), 2x10(-6), 2x10(-5), 1x10(-4) and 2x10(-4) M of LTD4 was injected into the rat ear. The severity of OME was assessed based on the histological findings. The concentrations of IL1-beta, TNF-alpha, and GRO/CINC-1 in MEE were also measured. Additionally the therapeutic efficacy of a specific LTs antagonist, pranlukast on experimental OME was investigated.


RESULTS
all ears developed middle ear effusion (MEE) within 24 h and about 50% of the animals continued to demonstrate MEE for 14 days in the 1x10(-4) and 2x10(-4) M groups. The cytokine levels seemed to correspond well with the persistence of OME. The oral administration of a specific LTs antagonist, pranlukast, was found to alleviate the experimental OME.


CONCLUSIONS
these findings suggest that LTs appear to plays an important role in the pathogenesis of OME.
Tada
Naoki
N
Department of Otorhinolaryngology, Kansai Medical University, 10-15 Fumizono, 570-8506, Moriguchi, Japan. naoki-t@db3.so-net.ne.jp
Furukawa
Masayuki
M
Ogura
Manabu
M
Arai
Shoji
S
Adachi
Yasushi
Y
Ikehara
Susumu
S
Yamashita
Toshio
T
D000818:Animals; D002867:Chromones / Q000494:pharmacology* / Q000627:therapeutic use; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D020024:Leukotriene Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D017998:Leukotriene D4 / Q000633:toxicity*; D008297:Male; D023421:Models, Animal; D010034:Otitis Media with Effusion / Q000139:chemically induced* / Q000188:drug therapy / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012720:Severity of Illness Index
D002867:Chromones; D016207:Cytokines; D020024:Leukotriene Antagonists; D017998:Leukotriene D4; C047681:pranlukast