Early intervention with suplatast tosilate for prophylaxis of pediatric atopic asthma: A pilot study

Abstract

The onset of asthma may be related to Th2 cytokine dominance at the time when food allergies occur several months after birth. This study investigated the effectiveness of early intervention with a Th2 cytokine inhibitor (suplatast tosilate) for prevention of asthma in infants with food allergies and atopic dermatitis. Suplatast tosilate dry syrup (6 mg/kg daily) or a histamine H(1)-blocker (ketotifen fumarate dry syrup: 0.06 mg/kg daily) was administered randomly to 53 infants with atopic dermatitis caused by food allergies. The primary endpoints were the incidence of asthma and the time to the onset of wheezing. The peripheral blood Th1/Th2 ratio, total IgE level, and eosinophil count were measured before and after treatment. After 24 months of treatment, the prevalence of asthma was significantly lower in the suplatast group (20.8%) than in the ketotifen group (65.6%, p < 0.01). Additionally, the time from the start of treatment to the initial episode of wheezing for infants who developed asthma was significantly longer in the suplatast group than the ketotifen group (p < 0.01). Furthermore, the eosinophil count was significantly decreased by suplatast treatment (p < 0.05), and there was a significant difference between the suplatast and ketotifen groups with respect to both the eosinophil count (p < 0.01) and the Th1/Th2 ratio (p < 0.05). The results of the present pilot study suggest that suplatast tosilate is useful for the primary prevention of wheezing and asthma in children.

Suplatast Tosilate Inhibits Histamine Signaling by Direct and Indirect Down-Regulation of Histamine H1 Receptor Gene Expression through Suppression of Histidine Decarboxylase and IL-4 Gene Transcriptions

“…It is well known that H 1 antihistamines inhibit histamine signal by their binding to H1R. Recently, Yoshihara et al investigated the effectiveness of early intervention with suplatast for prophylaxis of pediatric atopic asthma and compared the efficacy of suplatast with ketotifen, one of the H 1 antihistamines, and found that suplatast is more effective for the primary prevention of wheezing and asthma in children than ketotifen (57). Their findings can be explained by our data.…”

Effect of Histamine H₁ Receptor Antagonists on TARC/CCL17 and MDC/CCL22 Production from CD14+ Cells Induced by Antigenic Stimulation in vitro

“…We also demonstrated that FEX is the most effective agent in terms of the suppression of TARC and MDC production from CD14+ cells after Cry j 1 stimulation. This conclusion may be supported by the observation that FEX exerted a significant suppressive effect at a concentration of 250 ng/ml, which is almost equal to therapeutic blood levels [18], but other agents, AZE, KET and OXA, required higher concentrations (approximately 1.5–2 times higher) than their therapeutic blood levels [19,20,21]. …”

IL-4 and IL-12 Polymorphisms are Associated with Response to Suplatast Tosilate, a Th2 Cytokine Inhibitor, in Patients with Atopic Dermatitis

“…Suplatast tosilate has been reported to suppress IgE formation and eosinophil counts presumably through inhibition of Th2 cytokine in basic experiments and in several clinical studies in patients with atopic asthma [13][14][15][16][17][18][19][20]. However, no significant decreases in Th2-related parameters, such as the total IgE level and the eosinophil count, were observed after suplatast tosilate treatment even among the responders in this study.…”

“…This agent has been used as an adjunct to or in combination with topical anti-inflammatory and immunosuppressive agents and has been shown to reduce the requirements for these agents [11,12]. Suplatast tosilate has been referred to as a Th2 cytokine inhibitor because 1) it was discovered based on its capacity to suppress murine IgE formation without affecting cellular immune responses [13], 2) it suppressed IL-4 and IL-5 production by Th2 cells [14], 3) it suppressed allergic inflammation via indirect actions on Th2 cells as well as direct actions on eosinophils [15][16][17][18][19], and 4) it affected certain biomarkers such as Th1/Th2 ratio during the treatment of allergic asthmatic patients [20]. Although its mechanism of action remains to be identified at a molecular level, it is reasonable to assume that its efficacy in allergic patients may be ascribed to the modulation of the Th2-related immune and inflammatory responses.…”