Dataset Information

Pimecrolimus Is a Potent Inhibitor of Allergic Reactions to Hymenopteran Venom Extracts and Birch Pollen Allergen In Vitro.

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 Fc?RI-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 ?Mol 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.

SUBMITTER: Heneberg P

PROVIDER: S-EPMC4643035 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Pimecrolimus Is a Potent Inhibitor of Allergic Reactions to Hymenopteran Venom Extracts and Birch Pollen Allergen In Vitro.

Heneberg Petr P Riegerová Kamila K Kučera Petr P

PloS one 20151112 11

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 ( ...[more]

PMID: 26562153

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Project description:AimTo investigate whether birch pollen allergy symptoms are linked with gut microbiota changes and whether probiotics have an effect on these.MethodsForty seven children with confirmed birch pollen allergy were randomized to receive either a probiotic combination of Lactobacillus acidophilus (L. acidophilus) NCFM (ATCC 700396) and Bifidobacterium lactis (B. lactis) Bl-04 (ATCC SD5219) or placebo in a double-blind manner for 4 mo, starting prior to onset of the birch pollen season. Symptoms were recorded in a diary. Blood samples were taken for analysis of cytokines and eosinophils. Fecal samples were analysed for microbiota components, calprotectin and IgA. Nasal swabs were taken for analysis of eosinophils.ResultsThe pollen season induced a reduction in Bifidobacterium, Clostridium and Bacteroides which could not be prevented by the probiotic intervention. During the intervention, significantly higher numbers of B. lactis 11.2 x 10(7) +/- 4.2 x 10(7) vs 0.1 x 10(7) +/- 0.1 x 10(7) bacteria/g feces (P < 0.0001) and L. acidophilus NCFM 3.5 x 10(6) +/- 1.3 x 10(6) vs 0.2 x 10(6) +/- 0.1 x 10(6) bacteria/g feces (P < 0.0001) were observed in the probiotic group compared to the placebo group. During May, there was a tendency for fewer subjects, (76.2% vs 95.2%, P = 0.078) to report runny nose, while during June, fewer subjects, 11.1% vs 33.3%, reported nasal blocking in the probiotics group (P = 0.101). Concomitantly, fewer subjects in the probiotic group had infiltration of eosinophils in the nasal mucosa compared to the placebo group, 57.1% vs 95% (P = 0.013). Eye symptoms tended to be slightly more frequent in the probiotic group, 12.5 d [interquartile range (IQR) 6-18] vs 7.5 d (IQR 0-11.5) (P = 0.066) during May. Fecal IgA was increased in the placebo group during the pollen season; this increase was prevented by the probiotics (P = 0.028).ConclusionBirch pollen allergy was shown to be associated with changes in fecal microbiota composition. The specific combination of probiotics used was shown to prevent the pollen-induced infiltration of eosinophils into the nasal mucosa, and indicated a trend for reduced nasal symptoms.

Dataset Information

Pimecrolimus Is a Potent Inhibitor of Allergic Reactions to Hymenopteran Venom Extracts and Birch Pollen Allergen In Vitro.

Publications

Pimecrolimus Is a Potent Inhibitor of Allergic Reactions to Hymenopteran Venom Extracts and Birch Pollen Allergen In Vitro.

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