title: A rat model of exercise-induced asthma: a nonspecific response to a specific immunogen.
abstract: Exercise-induced bronchoconstriction (EIB) is common; however, key aspects of its pathogenesis are still unclear. We investigated the feasibility of adapting an established animal model of asthma to investigate the earliest stages of EIB. The hypothesis was that a single exposure to a normally innocuous, and brief, exercise challenge could trigger EIB symptoms in rats previously sensitized to ovalbumin (OVA) but otherwise unchallenged. Brown-Norway rats were sensitized by intraperitoneal injection of OVA at 0 and 2 wk. At week 3, animals were exposed to either aerosolized OVA (SS) or exercise (EXS). A trained, blinded, clinical observer graded EIB by respiratory sounds. Plasma and lung cytokine levels were analyzed. No control rats with or without exercise (EX, CON) showed evidence of EIB. Eighty percent of the SS group demonstrated abnormal breath sounds upon exposure to aerosolized OVA. Approximately 30% of EXS rats sensitized to OVA but exposed only to exercise had abnormal breath sounds. Lung tissue levels of TNF-α, IL-1α, growth-related oncogene/keratinocyte/chemoattractant, and IFN-γ were significantly higher (P < 0.001) in the SS group, relative to all other groups. Changes in most of these cytokines were not notable in the EXS rats, suggesting a different mechanism of EIB. Remarkably, IFN-γ, but not the other cytokines measured, was significantly elevated following brief exercise in both sensitized and unsensitized rats. Exercise led to detectable breathing sound abnormalities in sensitized rats, but less severe than those observed following classical OVA challenge. Precisely how this immune crossover occurs is not known, but this model may be useful in elucidating essential mechanisms of EIB.
authors.affiliation: Department of Pediatrics, University of California, Irvine, Irvine, California 92697-4560, USA.
authors.forename: Einat
authors.initials: E
authors.lastname: Kodesh
authors.forename: Frank
authors.initials: F
authors.lastname: Zaldivar
authors.forename: Christina
authors.initials: C
authors.lastname: Schwindt
authors.forename: Phuc
authors.initials: P
authors.lastname: Tran
authors.forename: Alvin
authors.initials: A
authors.lastname: Yu
authors.forename: Marinelle
authors.initials: M
authors.lastname: Camilon
authors.forename: Dwight M
authors.initials: DM
authors.lastname: Nance
authors.forename: Szu-Yun
authors.initials: SY
authors.lastname: Leu
authors.forename: Dan
authors.initials: D
authors.lastname: Cooper
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Adams
mesh_terms: D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology*; D016084:Bronchoconstriction / Q000502:physiology*; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D004195:Disease Models, Animal; D006632:Histamine / Q000378:metabolism; D007073:Immunoglobulin E / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009504:Neutrophils / Q000473:pathology; D010047:Ovalbumin / Q000009:adverse effects; D010805:Physical Conditioning, Animal / Q000502:physiology*; D051381:Rats; D011914:Rats, Inbred BN; D012135:Respiratory Sounds / Q000502:physiology
chemical_list: D016207:Cytokines; D007073:Immunoglobulin E; D006632:Histamine; D010047:Ovalbumin