Suplatast tosilate inhibits goblet-cell metaplasia of airway epithelium insensitized mice

Background: IL-4 and IL-13 play a putative role in mucus hypersecretion in asthma. Suplatast tosilate prevents the synthesis of T-H2 cytokines. Objective: Because suplatast tosilate inhibits T-H2 cytokines but does not inhibits IFN-gamma production, we examined the effect of suplatast on IL-4- or IL-13- and ovalbumin (OVA)-induced mucin synthesis in NCI-H292 cells in vitro and in bronchi of pathogen-free BALB/c mice in vivo. Methods: In vitro, NCI-H292 cells were preincubated with suplatast tosilate (0.1-100 mu g/mL) 1 hour before adding human recombinant IL-4 (10 ng/mL). In vivo, mouse recombinant IL-4 or IL-13 (250 ng per/mouse) was instilled i ntranasally in mice pretreated with suplatast tosilate (50 mg(.)kg(-1.)d(-1 )). Mucous glycoconjugates were stained with Alcian blue (AB)/periodic acid -Schiff (PAS) stain. To evaluate effects of suplatast tosilate on goblet-ce ll metaplasia in OVA-sensitized mice, animals were pretreated with suplatas t tosilate (1-50 mg(.)kg(-1.)d(-1)) intragastrically, IL-4 and IL-13 were m easured, and allergic inflammatory cells were analyzed in bronchoalveolar l avage fluid of OVA-sensitized mice. Results: Pretreatment with suplastast did not prevent IL-4- or IL-13-induce d increase in mucous glycoconjugate production in NCI-H292 cells or in mice . OVA sensitization increased AB/PAS-stained area of the epithelium (48.1% +/- 2.4%, P < .01 compared with control mice). Suplatast tosilate inhibited OVA-induced goblet-cell metaplasia in airway epithelium in a dose-dependen t fashion; 50 mg(.)kg(-1.)d(-1) decreased the AB/PAS area to 22.7% +/- 2.7% (P < .05 compared with OVA sensitization alone). Pre-treatment with suplat ast tosilate also prevented OVA-induced increase in IL-4 and IL-13 levels a nd decreased the number of lymphocytes and eosinophils in bronchoalveolar l avage fluid (P < .05 compared with values of mice given OVA alone), Conclusion: These results indicate that suplatast tosilate prevents allerge n-induced goblet-cell metaplasia and the recruitment of eosinophils and lym phocytes into the airways, These results suggest that this effect is due to the prevention of the production of T-H2 cytokines in airways.