Non-IgE-mediated hypersensitivity induced by multivitamins containing Tween-80

Multivitamins have been widely used for years. 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-80 and vial 2. Multivitamins without Tween-80 were used as a contrast. Behaviouristics, histamine, IgE, and blood pressure of beagle dogs and guinea-pigs were investigated by observation, ELISA and sphygmomanometer, and degranulation and apoptotic of RBL-2H3 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-80, compared to the control, multivitamins vial 2 or multivitamins without Tween-80. In anaphylaxis assay, guinea-pigs 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-80 groups except ovalbumin. Compared to the control, the release of beta-hexosaminidase and histamine, and the apoptosis of non-antigen-sensitized RBL-2H3 cells significantly increased in the Tween-80 and multivitamins and multivitamins vial 1 groups in a concentration-dependent manner. However, there was no alteration in multivitamins vial 2 and multivitamins without Tween-80 groups. The results indicate that the hypersensitivity induced by multivitamins may be anaphylactoid reaction, but not anaphylaxis. Multivitamin-induced release of inflammatory factors is triggered by Tween-80 through a non-IgE-mediated pathway.