Print Email Facebook Twitter The evaluation of the immunomodulating properties of ERA-63 a pharmaceutical with estrogenic activity Title The evaluation of the immunomodulating properties of ERA-63 a pharmaceutical with estrogenic activity Author Janssen, G.B. Penninks, A.H. Knippels, L.M.J. van Zijverden, M. Spanhaak, S. TNO Kwaliteit van Leven Publication year 2008 Abstract This paper describes studies performed with ERA-63 a low molecular weight pharmaceutical with intended immunomodulatory effects. Since this compound was also known to have estrogenic activity a non-conventional approach was taken in order to differentiate between estrogenic and non-estrogenic-induced immunomodulatory effects. EE was included not only for qualitative comparison (hazard identification) between immunomodulatory effects but also, in case of similar effects, to facilitate the extrapolation of the findings in the rat to anticipated effects in humans. After 28 days of treatment with dosages ranging from pharmacological up to clearly toxic levels for both compounds the immunotoxic potential was assessed by performing a T cell-dependent antibody response and a host resistance assay in rats. Selected ERA-63 dose levels (0.167-0.2, 1.67-2 and 16.7-20 mg/kg) were expected to have comparable estrogenic activity to respective EE dose levels (0.05, 0.5 and 5 mg/kg). General toxicity parameters reflecting estrogenic activity (i.e. decreased body- and organ weights of thymus and testis, and increased bilirubin and GGT levels) confirmed the comparable estrogenic activity for both compounds at the dose levels tested. Together with the comparable estrogen-related immune suppression (i.e. decreases in specific antibody responses and an increased susceptibility for Listeria monocytogenes infects) for both compounds, this indicates that available clinical data for EE facilitates the human risk assessment of ERA-63. © 2008 Elsevier Ireland Ltd. All rights reserved. Subject ChemistryEthinyl estradiolHost resistanceImmunotoxicityListeria monocytogenesPFCPlaque-forming cell assayT cell-dependent antibody responsebilirubinera 63ethinylestradiolgamma glutamyltransferaseimmunomodulating agentunclassified druganimal experimentantibody responsearticlebilirubin blood levelbody weightcontrolled studydrug dose comparisondrug megadosedrug screeningestrogen activityfemalegamma glutamyl transferase blood levelimmunomodulationListeria monocytogeneslow drug dosemalenonhumanpriority journalqualitative analysisrattestis weightthymusAnimalsAntibody FormationBody WeightEstrogensEthinyl EstradiolFemaleHemolytic Plaque TechniqueImmunologic FactorsListeria InfectionsMaleOrgan SizeRatsRats, Sprague-DawleyRisk AssessmentT-LymphocytesListeria monocytogenesRattus To reference this document use: http://resolver.tudelft.nl/uuid:cec2faa9-ffe2-4310-86b2-1d627711e851 DOI https://doi.org/10.1016/j.toxlet.2008.06.857 TNO identifier 240965 ISSN 0378-4274 Source Toxicology Letters, 180 (3), 196-201 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.