Nasal blockage induced by oral administration of non-steroidal anti-inflammatory drugs in a guinea-pig model of allergic rhinitis.
To elucidate the mechanisms underlying nasal symptoms in patients with aspirin hypersensitivity, we evaluated the effects of orally administered non-steroidal anti-inflammatory drugs (NSAIDs) on the nasal patency of guinea pigs with cedar pollen-induced chronic allergic rhinitis. Indomethacin (10 mg/kg) administered 1 h before a pollen challenge amplified the antigen-induced nasal blockage. More interestingly, even in the absence of the pollen challenge, indomethacin induced nasal blockage at 30 min at 4 h after administration. However, indomethacin-induced nasal blockage was not provoked in non-sensitized animals. Another NSAID, diclofenac (30 mg/kg), also evoked nasal blockage, but unexpectedly, aspirin (500 mg/kg) did not affect nasal patency. Indomethacin-induced nasal blockage was unaffected by a cysteinyl leukotriene receptor (CysLT(1) receptor) antagonist, pranlukast (30 mg/kg, p.o.), or by prostaglandin E2 (10(-3) M, intranasal), suggesting that the nasal blockage may not be due to hyperproduction of cysteinyl leukotrienes or inhibition of prostaglandin E2 production. These results indicate that the indomethacin-induced nasal blockage may not be an identical phenomena to airway symptoms in aspirin hypersensitivity patients. However, because chronic nasal inflammation is indispensable for the development of nasal blockage, indomethacin-induced nasal blockage may become a clue to elucidate new mechanisms underlying hypersensitivity to NSAIDs.
Han
Hai Yan
HY
Department of Pharmacology, Kyoto Pharmaceutical University, 5 Nakauchi. Misasagi, Yamashina, Kyoto 607-8414, Japan.
Nabe
Takeshi
T
Mizutani
Nobuaki
N
Fujii
Masanori
M
Terada
Tetsuya
T
Takenaka
Hiroshi
H
Kohno
Shigekatsu
S
D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001241:Aspirin / Q000009:adverse effects; D002867:Chromones / Q000494:pharmacology; D004008:Diclofenac / Q000009:adverse effects; D015232:Dinoprostone / Q000494:pharmacology; D004195:Disease Models, Animal; D006168:Guinea Pigs; D007213:Indomethacin / Q000009:adverse effects; D008297:Male; D015508:Nasal Obstruction / Q000139:chemically induced*; D012221:Rhinitis, Allergic, Perennial / Q000150:complications*; D006255:Rhinitis, Allergic, Seasonal / Q000150:complications*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002867:Chromones; D004008:Diclofenac; D015232:Dinoprostone; D001241:Aspirin; C047681:pranlukast; D007213:Indomethacin