title: Effects of combination therapy with montelukast and carbocysteine in allergen-induced airway hyperresponsiveness and airway inflammation.
abstract: OBJECTIVE
  Montelukast and S-carbocysteine have been used in asthmatic patients as an anti-inflammatory or mucolytic agent respectively. S-carbocysteine also exhibits anti-inflammatory properties.
  
  
  METHODS
  Ovalbumin (OVA) sensitized BALB/c mice were challenged with OVA for 3 days followed by single OVA re-challenge (secondary challenge) 2 weeks later. Forty-eight hours after secondary challenge, mice were assessed for airway hyperresponsiveness (AHR) and cell composition in bronchoalveolar lavage (BAL) fluid. Suboptimal doses of 10 mg.kg(-1) of S-carbocysteine by intraperitoneal injection (ip), 20 mg.kg(-1) of montelukast by gavage, the combination of S-carbocysteine and montelukast or 3 mg.kg(-1) of dexamethasone as a control were administered from 1 day before the secondary challenge to the last experimental day. Isolated lung cells were cultured with OVA and montelukast to determine the effects on cytokine production.
  
  
  RESULTS
  Treatment with S-carbocysteine or montelukast reduced both AHR and the numbers of eosinophils in BAL fluid. Neutralizing IFN-gamma abolished the effects of S-carbocysteine on these airway responses. Combination of the two drugs showed further decreases in both AHR and eosinophils in the BAL fluid. Goblet cell metaplasia and Th2-type cytokines, interleukin (IL)-4, IL-5 and IL-13, in BAL fluid were decreased with montelukast treatment. Conversely, S-carbocysteine increased Th1-type cytokines, IFN-gamma and IL-12 in BAL fluid.
  
  
  CONCLUSIONS
  The combination of two agents, montelukast and S-carbocysteine, demonstrated additive effects on AHR and airway inflammation in a secondary allergen model most likely through independent mechanisms of action.
authors.affiliation: Department of Pediatrics, National Jewish Health, Denver, CO, USA.
authors.forename: K
authors.initials: K
authors.lastname: Takeda
authors.forename: Y
authors.initials: Y
authors.lastname: Shiraishi
authors.forename: S
authors.initials: S
authors.lastname: Matsubara
authors.forename: N
authors.initials: N
authors.lastname: Miyahara
authors.forename: H
authors.initials: H
authors.lastname: Matsuda
authors.forename: M
authors.initials: M
authors.lastname: Okamoto
authors.forename: A
authors.initials: A
authors.lastname: Joetham
authors.forename: E W
authors.initials: EW
authors.lastname: Gelfand
mesh_terms: D000085:Acetates / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology; D016535:Bronchial Hyperreactivity / Q000188:drug therapy* / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid; D002233:Carbocysteine / Q000008:administration & dosage / Q000494:pharmacology*; D003521:Cyclopropanes; D003907:Dexamethasone / Q000494:pharmacology; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004804:Eosinophils / Q000378:metabolism; D005260:Female; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology; D007274:Injections, Intraperitoneal; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D011804:Quinolines / Q000008:administration & dosage / Q000494:pharmacology*; D013440:Sulfides
chemical_list: D000085:Acetates; D018927:Anti-Asthmatic Agents; D000893:Anti-Inflammatory Agents; D003521:Cyclopropanes; D011804:Quinolines; D013440:Sulfides; D002233:Carbocysteine; D003907:Dexamethasone; D010047:Ovalbumin; C093875:montelukast