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Adverse reactions, especially hypersensitivity, to multivitamins are becoming noteworthy. However, the classification of hypersensitivity is confusing, and the trigger is unknown. Multivitamins consist of two vials labelled vial 1 containing Tween\u201080 and vial 2. Multivitamins without Tween\u201080 were used as a contrast. Behaviouristics, histamine, IgE, and blood pressure of beagle dogs and guinea\u2010pigs were investigated by observation, <jats:styled-content style=\"fixed-case\">ELISA<\/jats:styled-content> and sphygmomanometer, and degranulation and apoptotic of <jats:styled-content style=\"fixed-case\">RBL<\/jats:styled-content>\u20102H3 cells were assayed by spectrophotometry and flow cytometry. The results showed that dogs suffered from multiorgan anaphylactoid symptoms, and dramatically decreased blood pressure, and high plasma concentrations of histamine after the first administration of multivitamins and multivitamins vial 1, which contains Tween\u201080, compared to the control, multivitamins vial 2 or multivitamins without Tween\u201080. In anaphylaxis assay, guinea\u2010pigs did not display any anaphylaxis symptoms and there were no changes in plasma histamine and IgE concentrations in the multivitamins and multivitamins vial 1 groups or in the multivitamins vial 2 and multivitamins without Tween\u201080 groups except ovalbumin. Compared to the control, the release of \u03b2\u2010hexosaminidase and histamine, and the apoptosis of non\u2010antigen\u2010sensitized <jats:styled-content style=\"fixed-case\">RBL<\/jats:styled-content>\u20102H3 cells significantly increased in the Tween\u201080 and multivitamins and multivitamins vial 1 groups in a concentration\u2010dependent manner. However, there was no alteration in multivitamins vial 2 and multivitamins without Tween\u201080 groups. The results indicate that the hypersensitivity induced by multivitamins may be anaphylactoid reaction, but not anaphylaxis. Multivitamin\u2010induced release of inflammatory factors is triggered by Tween\u201080 through a non\u2010IgE\u2010mediated pathway.<\/jats:p>","DOI":"10.1111\/1440-1681.13089","type":"journal-article","created":{"date-parts":[[2019,3,25]],"date-time":"2019-03-25T10:52:12Z","timestamp":1553511132000},"page":"664-675","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Non\u2010IgE\u2010mediated hypersensitivity induced by multivitamins containing Tween\u201080"],"prefix":"10.1111","volume":"46","author":[{"given":"Yan\u2010Ni","family":"Mi","sequence":"first","affiliation":[{"name":"Department of Pharmacology School of Basic Medical Sciences Xi'an Jiaotong University Health Science Center Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping\u2010Ping","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Basic Medical Sciences Xi'an Jiaotong 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