Effects of nonsteroidal anti-inflammatory drugs on experimental allergic conjunctivitis in Guinea pigs.
The effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on experimental allergic conjunctivitis, induced by ocular challenge with antigen in actively sensitized guinea pigs, were investigated. NSAIDs reduced the increase in prostaglandin D2 (PGD2) and E2 (PGE2) in the ocular lavage fluid. The inhibition of NSAIDs to these increases was approximately 90%-95%. NSAIDs also lowered itch-scratch response (ISR) to approximately one-third to one-half of the vehicle-treated group. However, these drugs scarcely affected plasma exudation in the conjunctiva. Ketotifen, an H1 histamine receptor antagonist, inhibited both pathophysiological changes (inhibition: 70%-80%). However, this drug was less efficacious than NSAIDs in reducing PGD2 and PGE2 levels. Moreover, topical administration of histamine induced ISR and plasma exudation; in contrast, PGD2 induced ISR exclusively. These results suggest that a part of antigen-induced ISR may be attributable to PGs. However, PGs may not play a key role in plasma exudation; other mediators such as histamine may be involved.
Hashimoto
Terumasa
T
Medical Research and Development Department, Sagami Research Laboratories, Wakamoto Pharmaceutical Co., Ltd. Tokyo, Japan. hashi@wakamoto-pharm.co.jp
Igarashi
Atsushi
A
Hoshina
Futoshi
F
Yamada
Mie
M
Toyoda
Yoshihiro
Y
Notsu
Yoshitada
Y
Kohno
Shigekatsu
S
D000287:Administration, Topical; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000941:Antigens / Q000008:administration & dosage / Q000009:adverse effects; D001577:Benzophenones / Q000493:pharmacokinetics; D001578:Benzopyrans / Q000008:administration & dosage / Q000493:pharmacokinetics; D001969:Bromobenzenes / Q000493:pharmacokinetics; D003233:Conjunctivitis, Allergic / Q000188:drug therapy* / Q000209:etiology; D004008:Diclofenac / Q000008:administration & dosage / Q000493:pharmacokinetics; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D004195:Disease Models, Animal; D005070:Evans Blue; D005122:Exudates and Transudates / Q000737:chemistry; D005123:Eye / Q000187:drug effects; D006168:Guinea Pigs; D006632:Histamine / Q000008:administration & dosage / Q000009:adverse effects; D006636:Histamine Release / Q000187:drug effects; D007114:Immunization; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D007665:Ketotifen / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D008297:Male; D010047:Ovalbumin / Q000008:administration & dosage / Q000494:pharmacology; D011422:Propionates / Q000008:administration & dosage / Q000493:pharmacokinetics; D015230:Prostaglandin D2 / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D011537:Pruritus / Q000139:chemically induced / Q000517:prevention & control; D007507:Therapeutic Irrigation / Q000379:methods
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000941:Antigens; D001577:Benzophenones; D001578:Benzopyrans; D001969:Bromobenzenes; D011422:Propionates; D004008:Diclofenac; C043940:pyranoprofen; D005070:Evans Blue; D006632:Histamine; C053083:bromfenac; D010047:Ovalbumin; D015232:Dinoprostone; D015230:Prostaglandin D2; D007665:Ketotifen