title: Cysteinyl leukotriene-dependent interleukin-5 production leading to eosinophilia during late asthmatic response in guinea-pigs.
abstract: BACKGROUND
  Allergic airway eosinophilia is suppressed by cysteinyl leukotriene (CysLT) receptor (CysLT1 receptor) antagonists in several species including humans and guinea-pigs, suggesting that CysLTs are directly or indirectly involved in induction of the response.
  
  
  OBJECTIVE
  We examined the effect of CysLT antagonists (pranlukast and MCI-826) on antigen inhalation-induced eosinophilia in peripheral blood and lung, and on IL-5 activity in serum during late increase of airway resistance (late asthmatic response, LAR) in sensitized guinea-pigs.
  
  
  METHODS
  Guinea-pigs inhaled ovalbumin (OVA) + Al(OH)3 and OVA mists alternately for sensitization and challenge, respectively, once every 2 weeks. At the fifth challenge, the effects of CysLT antagonists and an anti-IL-5 antibody (TRFK-5) on the occurrence of LAR, and blood and lung eosinophilia, which appeared at 5 h after challenge, were examined. The time-course of IL-5 activity in the serum after the challenge was evaluated by measuring in vitro 'eosinophil survival prolongation activity'. The influence of CysLT antagonists on IL-5 activity was assessed.
  
  
  RESULTS
  CysLT antagonists and TRFK-5 completely abolished blood and lung eosinophilia. LAR was suppressed by both MCI-826 and TRFK-5 by 40-50%. Sera obtained from sensitized, challenged animals 3 h and 4 h after challenge induced an obvious prolongation of eosinophil survival. The activity of the sera was completely neutralized by prior exposure to TRFK-5, suggesting that it reflected IL-5 activity. Increased IL-5 activity in the serum was inhibited by both pranlukast and MCI-826 by over 90%.
  
  
  CONCLUSIONS
  CysLTs produced after antigen provocation sequentially induced IL-5 production from some immune component cells via CysLT1 receptor activation. Thus, it is likely that CysLTs indirectly cause antigen-induced eosinophilia through IL-5 production.
authors.affiliation: Department of Pharmacology, Kyoto Pharmaceutical University, Yamashina, Kyoto, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Nabe
authors.forename: K
authors.initials: K
authors.lastname: Yamashita
authors.forename: M
authors.initials: M
authors.lastname: Miura
authors.forename: T
authors.initials: T
authors.lastname: Kawai
authors.forename: S
authors.initials: S
authors.lastname: Kohno
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology*; D002470:Cell Survival / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D003545:Cysteine / Q000502:physiology*; D004802:Eosinophilia / Q000097:blood; D006168:Guinea Pigs; D015848:Interleukin-5 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000502:physiology; D007700:Kinetics; D020024:Leukotriene Antagonists / Q000494:pharmacology; D015289:Leukotrienes / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins; D010047:Ovalbumin / Q000276:immunology; D011657:Pulmonary Eosinophilia / Q000276:immunology*; D018077:Receptors, Leukotriene; D013844:Thiazoles / Q000494:pharmacology
chemical_list: D002867:Chromones; D015848:Interleukin-5; D020024:Leukotriene Antagonists; D015289:Leukotrienes; D008565:Membrane Proteins; D018077:Receptors, Leukotriene; D013844:Thiazoles; C112381:cysteinyl-leukotriene; C077265:MCI 826; D010047:Ovalbumin; C412375:cysteinyl leukotriene receptor 2; D003545:Cysteine; C083169:leukotriene D4 receptor; C047681:pranlukast