title: Modification of eosinophil function by suplatast tosilate (IPD), a novel anti-allergic drug.
abstract: Suplatast tosilate (IPD), a new dimethylsulfonium agent, is used therapeutically in allergic diseases. Suplatast has been reported to attenuate airway hyperresponsiveness in guinea pigs, human IgE synthesis, and murine peritoneal eosinophilia. However, the effect of suplatast on human eosinophils is not known. In this study, we examined the effects of suplatast in human eosinophils on platelet activating factor (PAF, 1 microM)-induced chemotaxis by the blind well chamber technique, eosinophil adhesion to TNF-alpha (10 ng/ml) or IL-4 (10 ng/ml)-stimulated human umbilical vein endothelial cells (HUVECs), and expression of very late antigen-4 (VLA-4) on eosinophils and vascular cell adhesion molecule-1 (VCAM-1) on HUVECs by flow cytometry. Suplatast suppressed IL-4-induced eosinophil adhesion to HUVECs in a dose-dependent manner. Eosinophils from the normal subjects did not express VLA-4. However, there was a significant increase (P < 0.01) in the basal expression of VLA-4 in allergic patients. PAF or IL-4 did not enhance VLA-4 expression on eosinophils, and there was no significant effect of suplatast on VLA-4 expression in allergic patients. Suplatast did not affect TNF-alpha-induced VCAM-1 expression. Interestingly, suplatast significantly suppressed IL-4 induced VCAM-1 expression on HUVECs and PAF-induced eosinophil chemotaxis. These data suggest that suplatast may modify eosinophil participation in airway inflammation by attenuating inflammatory mediators-induced chemotaxis and adhesion to endothelial cells, and thus might be useful in the treatment of bronchial asthma.
authors.affiliation: Department of Medicine, Center for Allergy, Asthma and Immunology, Creighton University School of Medicine, Omaha, NE 68178, USA.
authors.forename: T
authors.initials: T
authors.lastname: Suwaki
authors.forename: D K
authors.initials: DK
authors.lastname: Agrawal
authors.forename: R G
authors.initials: RG
authors.lastname: Townley
mesh_terms: D018926:Anti-Allergic Agents / Q000494:pharmacology*; D001190:Arylsulfonates / Q000494:pharmacology*; D001249:Asthma / Q000097:blood / Q000150:complications / Q000276:immunology; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D004804:Eosinophils / Q000187:drug effects* / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D039041:Integrin alpha4beta1; D016023:Integrins / Q000096:biosynthesis / Q000235:genetics; D015847:Interleukin-4 / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000494:pharmacology; D011657:Pulmonary Eosinophilia / Q000209:etiology / Q000517:prevention & control; D016201:Receptors, Lymphocyte Homing / Q000096:biosynthesis / Q000235:genetics; D012130:Respiratory Hypersensitivity / Q000097:blood / Q000150:complications / Q000276:immunology; D013452:Sulfonium Compounds / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics
chemical_list: D018926:Anti-Allergic Agents; D001190:Arylsulfonates; D039041:Integrin alpha4beta1; D016023:Integrins; D010972:Platelet Activating Factor; D016201:Receptors, Lymphocyte Homing; D013452:Sulfonium Compounds; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D015847:Interleukin-4; C073028:suplatast tosilate