title: Effects of anti-inflammatory therapies on recurrent and low-grade respiratory syncytial virus infections in a murine model of asthma.
abstract: BACKGROUND
  Recurrent and subclinical viral respiratory tract infections could immunologically exacerbate allergic airway inflammation. However, the most appropriate treatment for virus-induced asthma exacerbation is yet to be established. The effects of glucocorticoids in virus-induced acute asthma are controversial.
  
  
  OBJECTIVE
  To determine the effects of representative anti-inflammatory therapies for asthma--glucocorticoids and leukotriene receptor antagonists (LTRAs)--in mite allergen-sensitized and repeatedly low-grade respiratory syncytial virus (RSV)--infected mice.
  
  
  METHODS
  Dermatophagoides farinae-sensitized mice were inoculated twice with low-grade RSV and subcutaneously injected with either a glucocorticoid or an LTRA for 4 consecutive days. Lung inflammation, cytokine profiles, LT production, and viral RNA in lung tissues were compared in 5 groups of 8 mice each: controls, D farinae allergen sensitized, D farinae sensitized and RSV infected, D farinae sensitized and RSV infected with dexamethasone, and D farinae sensitized and RSV infected with pranlukast, an LTRA.
  
  
  RESULTS
  Allergic airway inflammation in D farinae mice was significantly enhanced by recurrent and low-grade RSV infections (RLRIs). The glucocorticoid attenuated allergic airway inflammation, which was associated with interleukin 5 (IL-5) and interferon-gamma (IFN-gamma) suppression in lung-draining lymph nodes without affecting viral quantity. The LTRA also attenuated allergic airway inflammation in D farinae-RSV mice with concomitant inhibition of IL-5 but not IFN-gamma. Dermatophagoides farinae allergen sensitization significantly increased LTs in the airway, whereas RLRIs did not further enhance LT production.
  
  
  CONCLUSIONS
  Glucocorticoids and LTRAs significantly inhibit RLRI-induced exacerbation of allergic airway inflammation by distinct pathways. Dexamethasone suppressed nonspecific cytokines, whereas viral RNA did not increase via suppression of immunity. In contrast, pranlukast specifically inhibited IL-5 but not IFN-gamma.
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan. hmatsuse@net.nagasaki-u.ac.jp
authors.forename: Hiroto
authors.initials: H
authors.lastname: Matsuse
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kondo
authors.forename: Ikuko
authors.initials: I
authors.lastname: Machida
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kawano
authors.forename: Sachiko
authors.initials: S
authors.lastname: Saeki
authors.forename: Shinya
authors.initials: S
authors.lastname: Tomari
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Obase
authors.forename: Chizu
authors.initials: C
authors.lastname: Fukushima
authors.forename: Yohei
authors.initials: Y
authors.lastname: Mizuta
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kohno
mesh_terms: D000208:Acute Disease; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D039741:Antigens, Dermatophagoides / Q000276:immunology / Q000633:toxicity; D001249:Asthma / Q000188:drug therapy / Q000209:etiology* / Q000517:prevention & control; D001992:Bronchoalveolar Lavage Fluid; D002867:Chromones / Q000494:pharmacology / Q000627:therapeutic use*; D016207:Cytokines / Q000378:metabolism; D040001:Dermatophagoides farinae / Q000276:immunology; D003907:Dexamethasone / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D007249:Inflammation; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D015848:Interleukin-5 / Q000096:biosynthesis / Q000235:genetics; D020024:Leukotriene Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D015289:Leukotrienes / Q000096:biosynthesis / Q000235:genetics; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008198:Lymph Nodes / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D012008:Recurrence; D018357:Respiratory Syncytial Virus Infections / Q000150:complications*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D039741:Antigens, Dermatophagoides; D002867:Chromones; D016207:Cytokines; D015848:Interleukin-5; D020024:Leukotriene Antagonists; D015289:Leukotrienes; D003907:Dexamethasone; D007371:Interferon-gamma; C047681:pranlukast