title: S-carboxymethylcysteine normalises airway responsiveness in sensitised and challenged mice.
abstract: S-carboxymethylcysteine (S-CMC) has been used as a mucoregulator in respiratory diseases. However, the mechanism of action of S-CMC on allergic airway inflammation has not yet been defined. In the present study, BALB/c mice were initially sensitised and challenged to ovalbumin (OVA) and, weeks later, re-challenged with OVA (secondary challenge). S-CMC (5-100 mg.kg-1) was administered from 2 days before the secondary challenge through to the day of assay. Mice developed airway hyperresponsiveness (AHR) 6 h after the secondary challenge and increased numbers of neutrophils were present in the bronchoalveolar lavage (BAL) fluid. At 72 h after secondary challenge, mice again developed AHR, but the BAL fluid contained large numbers of eosinophils. S-CMC treatment was found to reduce AHR and neutrophilia at 6 h, as well as eosinophilia and AHR at 72 h. These effects appeared to be dose dependent. Goblet cell hyperplasia, observed at 72 h, was reduced by S-CMC. In BAL fluid, increased levels of interferon-gamma, interleukin (IL)-12 and IL-10 and decreased levels of IL-5 and IL-13 were detected. In conclusion, the data indicate that S-carboxymethylcysteine is effective in reducing airway hyperresponsiveness and airway inflammation at two distinct phases of the response to the secondary allergen challenge in sensitised mice.
authors.affiliation: Department of Paediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA.
authors.forename: K
authors.initials: K
authors.lastname: Takeda
authors.forename: N
authors.initials: N
authors.lastname: Miyahara
authors.forename: T
authors.initials: T
authors.lastname: Kodama
authors.forename: C
authors.initials: C
authors.lastname: Taube
authors.forename: A
authors.initials: A
authors.lastname: Balhorn
authors.forename: A
authors.initials: A
authors.lastname: Dakhama
authors.forename: K
authors.initials: K
authors.lastname: Kitamura
authors.forename: A
authors.initials: A
authors.lastname: Hirano
authors.forename: M
authors.initials: M
authors.lastname: Tanimoto
authors.forename: E W
authors.initials: EW
authors.lastname: Gelfand
mesh_terms: D000485:Allergens / Q000009:adverse effects; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000276:immunology / Q000627:therapeutic use*; D016535:Bronchial Hyperreactivity / Q000188:drug therapy* / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002233:Carbocysteine / Q000276:immunology / Q000627:therapeutic use*; D016207:Cytokines / Q000032:analysis; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000009:adverse effects
chemical_list: D000485:Allergens; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D002233:Carbocysteine; D010047:Ovalbumin