title: Histamine-induced cytokine production and ICAM-1 expression in human conjunctival fibroblasts.
abstract: OBJECTIVE
  Conjunctival fibroblasts stimulated with histamine (H) may be directly involved in the inflammatory and remodeling processes of chronic allergic conjunctival diseases.
  
  
  METHODS
  Proinflammatory cytokine and growth factor production, and the expression of intercellular adhesion molecule-1 (ICAM-1) were studied in conjunctival fibroblast cultures challenged with different concentrations of H (from 10(-9) M to 10(-) (4) M). Interleukin (IL)-1, IL-4, IL-6, IL-8, tumor necrosis factor-alfa (TNF-alpha), fibroblast growth factor (FGF), epidermal growth factor (EGF) and transforming growth factor-beta (TGFbeta-1) were measured in supernatants. ICAM-1 expression was evaluated by a fluorescence activated cell sorter (FACS). Inhibitory effects of the H-1 antagonists (antiH): emedastine, levocabastine, and azelastine, and of the antiH-2, cimetidine, on H-stimulated fibroblasts were evaluated by measuring both cytokines in supernatants and the cellular expression of ICAM-1.
  
  
  RESULTS
  Histamine increased the production of IL-1, IL-6 and IL-8, and ICAM-1 expression. TNF-alpha, IL-4 and growth factor production were not modified by histamine. The antiH-1, emedastine, significantly reduced H-induced production of IL-1, IL-6 and IL-8, while azelastine reduced only IL-1. Levocabastine and cimetidine were less effective. The histamine-induced increase in ICAM-1 expression was inhibited by emedastine but not by azelastine and levocabastine.
  
  
  CONCLUSIONS
  Histamine has pro-inflammatory effects on conjunctival fibroblasts, inducing the production of cytokines and the expression of ICAM-1. Emedastine significantly reduced cytokine and ICAM-1 expression from H-stimulated fibroblasts. Conjunctival fibroblasts may contribute to the maintenance of inflammation in chronic allergic diseases.
authors.affiliation: Department of Ophthalmology and Inflammatory Eye Diseases, University of Padua, Padua, Italy. mdvol@tin.it
authors.forename: Andrea
authors.initials: A
authors.lastname: Leonardi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: DeFranchis
authors.forename: Massimo
authors.initials: M
authors.lastname: De Paoli
authors.forename: Iva
authors.initials: I
authors.lastname: Fregona
authors.forename: Mario
authors.initials: M
authors.lastname: Plebani
authors.forename: Antonio
authors.initials: A
authors.lastname: Secchi
mesh_terms: D002478:Cells, Cultured; D003228:Conjunctiva / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D006632:Histamine / Q000494:pharmacology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*
chemical_list: D016207:Cytokines; D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D018799:Intercellular Adhesion Molecule-1; D006632:Histamine