title: Control of IL-5 production by human helper T cells as a treatment for eosinophilic inflammation: comparison of in vitro and in vivo effects between selective and nonselective cytokine synthesis inhibitors.
abstract: BACKGROUND
  Helper T cells are involved in the pathophysiologic condition of asthma, so modulation of cytokine production may be effective therapy.
  
  
  OBJECTIVE
  We aimed to selectively control the synthesis of IL-5 by helper T cells and tested in vivo effects using a murine asthma model.
  
  
  METHODS
  The effect of dexamethasone, FK506, cyclosporin A, and nonactin (a macrolide compound produced by Streptomyces griseus) on cytokine production by allergen-specific T-cell clones was determined. The effect of these agents and an anti-IL-5 neutralizing antibody on airway eosinophilic inflammation was investigated in a murine asthma model.
  
  
  RESULTS
  Dexamethasone, FK506, and cyclosporin A suppressed the production of IL-2, IL-4, and IL-5 by human helper T cells, which shows a similar concentration-response relationship in each case. Cyclosporin A and dexamethasone inhibited airway eosinophilia in vivo. Nonactin suppressed IL-5 synthesis but not IL-2 or IL-4 synthesis, and it also significantly suppressed airway eosinophilia.
  
  
  CONCLUSIONS
  Nonactin only suppressed IL-5 synthesis and was as effective against eosinophilia as cyclosporin A and dexa-methasone, which indicates that IL-5 is a reasonable therapeutic target in allergic disorders that are accompanied by eosinophilic inflammation.
authors.affiliation: Clinical Research Center for Allergy and Rheumatology, National Sagamihara Hospital, Discovery Research Laboratory, Tanabe Seiyaku Co Ltd, Toda, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Mori
authors.forename: O
authors.initials: O
authors.lastname: Kaminuma
authors.forename: K
authors.initials: K
authors.lastname: Ogawa
authors.forename: A
authors.initials: A
authors.lastname: Nakata
authors.forename: R W
authors.initials: RW
authors.lastname: Egan
authors.forename: K
authors.initials: K
authors.lastname: Akiyama
authors.forename: H
authors.initials: H
authors.lastname: Okudaira
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001249:Asthma / Q000517:prevention & control; D002999:Clone Cells; D016572:Cyclosporine / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004802:Eosinophilia / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007249:Inflammation / Q000188:drug therapy*; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000627:therapeutic use*; D018942:Macrolides / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism; D016559:Tacrolimus / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D015848:Interleukin-5; D018942:Macrolides; D015847:Interleukin-4; D003907:Dexamethasone; D016572:Cyclosporine; C050476:nonactin; D016559:Tacrolimus