Histamine-induced cytokine production and ICAM-1 expression in human conjunctival fibroblasts.
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.
Leonardi
Andrea
A
Department of Ophthalmology and Inflammatory Eye Diseases, University of Padua, Padua, Italy. mdvol@tin.it
DeFranchis
Giuseppe
G
De Paoli
Massimo
M
Fregona
Iva
I
Plebani
Mario
M
Secchi
Antonio
A
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*
D016207:Cytokines; D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D018799:Intercellular Adhesion Molecule-1; D006632:Histamine