title: The immunomodulatory actions of prostaglandin E2 on allergic airway responses in the rat.
abstract: PGE(2) has been reported to inhibit allergen-induced airway responses in sensitized human subjects. The aim of this study was to investigate the mechanism of anti-inflammatory actions of PGE(2) in an animal model of allergic asthma. BN rats were sensitized to OVA using Bordetella pertussis as an adjuvant. One week later, an aerosol of OVA was administered. After a further week, animals were anesthetized with urethan, intubated, and subjected to measurements of pulmonary resistance (R(L)) for a period of 8 h after OVA challenge. PGE(2) (1 and 3 micro g in 100 micro l of saline) was administered by insufflation intratracheally 30 min before OVA challenge. The early response was inhibited by PGE(2) (3 micro g). The late response was inhibited by both PGE(2) (1 and 3 micro g). Bronchoalveolar lavage fluid from OVA-challenged rats showed eosinophilia and an increase in the number of cells expressing IL-4 and IL-5 mRNA. These responses were inhibited by PGE(2). Bronchoalveolar lavage fluid levels of cysteinyl-leukotrienes were elevated after OVA challenge and were reduced after PGE(2) to levels comparable with those of sham challenged animals. We conclude that PGE(2) is a potent anti-inflammatory agent that may act by reducing allergen-induced Th2 cell activation and cysteinyl-leukotriene synthesis in the rat.
authors.affiliation: Meakins Christie Laboratories, Department of Medicine, McGill University, Montreal, Quebec, Canada. james.martin@mcgill.ca
authors.forename: James G
authors.initials: JG
authors.lastname: Martin
authors.forename: Masaru
authors.initials: M
authors.lastname: Suzuki
authors.forename: Karim
authors.initials: K
authors.lastname: Maghni
authors.forename: Rosa
authors.initials: R
authors.lastname: Pantano
authors.forename: David
authors.initials: D
authors.lastname: Ramos-Barbón
authors.forename: Daizo
authors.initials: D
authors.lastname: Ihaku
authors.forename: François
authors.initials: F
authors.lastname: Nantel
authors.forename: Danielle
authors.initials: D
authors.lastname: Denis
authors.forename: Qutayba
authors.initials: Q
authors.lastname: Hamid
authors.forename: William S
authors.initials: WS
authors.lastname: Powell
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000280:Administration, Inhalation; D000336:Aerosols; D000403:Airway Resistance / Q000187:drug effects / Q000276:immunology; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D003545:Cysteine / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015232:Dinoprostone / Q000008:administration & dosage / Q000494:pharmacology*; D006968:Hypersensitivity, Delayed / Q000276:immunology / Q000503:physiopathology; D006969:Hypersensitivity, Immediate / Q000276:immunology / Q000503:physiopathology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics; D015848:Interleukin-5 / Q000096:biosynthesis / Q000235:genetics; D007442:Intubation, Intratracheal; D007958:Leukocyte Count; D015289:Leukotrienes / Q000096:biosynthesis; D008297:Male; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D011650:Pulmonary Alveoli / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011914:Rats, Inbred BN; D018078:Receptors, Prostaglandin E / Q000378:metabolism; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000503:physiopathology
chemical_list: D000276:Adjuvants, Immunologic; D000336:Aerosols; D015848:Interleukin-5; D015289:Leukotrienes; D012333:RNA, Messenger; D018078:Receptors, Prostaglandin E; C112381:cysteinyl-leukotriene; D015847:Interleukin-4; D007371:Interferon-gamma; D010047:Ovalbumin; D015232:Dinoprostone; D003545:Cysteine