The immunomodulatory actions of prostaglandin E2 on allergic airway responses in the rat.
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.
Martin
James G
JG
Meakins Christie Laboratories, Department of Medicine, McGill University, Montreal, Quebec, Canada. james.martin@mcgill.ca
Suzuki
Masaru
M
Maghni
Karim
K
Pantano
Rosa
R
Ramos-Barbón
David
D
Ihaku
Daizo
D
Nantel
François
F
Denis
Danielle
D
Hamid
Qutayba
Q
Powell
William S
WS
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
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