Abstract
Pimecrolimus (Elidel, SDZ ASM 981) is an anti-inflammatory and immunomodulatory 33-epichloro-derivative of macrolactam ascomycin, with low potential for affecting systemic immune responses compared with other calcineurin inhibitors, cyclosporin A and tacrolimus. Despite numerous studies focused on the mechanism of pimecrolimus action on mast cells, only the single report has addressed pimecrolimus effects on other typical FcεRI-expressing cells, the basophils. Patients allergic to birch pollen (n = 20), hymenopteran venoms (n = 23) and 10 non-allergic volunteers were examined. Primary human basophils pre-treated or not with 0.5–50 μMol pimecrolimus were exposed to various concentrations of recombinant Bet v 1a allergen, bee or wasp venom extracts and anti-IgE for 20 min, and then examined for the expression of CD45, CD193, CD203c, CD63 and CD164 using flow cytometry. The externalization of basophil activation markers (CD63 and CD164) was equally inhibited through pimecrolimus in cells activated by recombinant pollen allergen, hymenopteran venom extracts and anti-IgE. Although the individual response rate was subject to strong variation, importantly, pre-treatment with pimecrolimus lowered the number of activated basophils in response to any of the stimuli in the basophils from all patients. The inhibition was concentration-dependent; approximately half of the basophils were inhibited in the presence of 2.5 mMol pimecrolimus. Pimecrolimus is a valuable new tool for the inhibition of hyper-reactive basophils in patients with pollen allergy and a history of anaphylactic reactions to bee or wasp venoms. Further research should address short-term use of pimecrolimus in vivo in a wide spectrum of allergic diseases.
Highlights
Over the last three decades, the rates of asthma and allergic diseases have increased worldwide, with over half of the U.S population aged 6 to 59 years sensitive to one or more allergens [1]
Preincubation of primary human basophils with pimecrolimus resulted in a dose-dependent inhibition of basophil activation, revealed as down-regulated CD63 externalization
The inhibition of CD63 externalization on ~50% of basophils was obtained using 2.5 μMol pimecrolimus (Fig 3); this concentration was used throughout the remainder of the study
Summary
Over the last three decades, the rates of asthma and allergic diseases have increased worldwide, with over half of the U.S population aged 6 to 59 years sensitive to one or more allergens [1]. Pimecrolimus as the Basophil Activation Inhibitor does not alter the authors' adherence to PLOS ONE policies on sharing data and materials. Central and Eastern Europe, the most allergenic tree pollen is produced by birch (Betula) [4,5], inducing locally highly prevalent pollen allergies, with a prevalence of up to 54% of the general population, such as in Zurich [4]. The frequency of severe anaphylaxis to venom, drug and food allergens is 1–3:10,000 persons, and is lethal in 0.65 to 2% of patients [11]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
