{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,26]],"date-time":"2026-04-26T09:31:18Z","timestamp":1777195878098,"version":"3.51.4"},"reference-count":50,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,5,31]],"date-time":"2020-05-31T00:00:00Z","timestamp":1590883200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["FOR 1328"],"award-info":[{"award-number":["FOR 1328"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SCHE 341\/17\u20101"],"award-info":[{"award-number":["SCHE 341\/17\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SCHE 341\/17\u20102"],"award-info":[{"award-number":["SCHE 341\/17\u20102"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:p>The rapamycin analogue everolimus (EVR) is a potent inhibitor of the mammalian target of rapamycin (mTOR) and clinically used to prevent allograft rejections as well as tumor growth. The pharmacokinetic and immunosuppressive efficacy of EVR have been extensively reported in patient populations and <jats:italic>in vitro<\/jats:italic> studies. However, dose\u2010dependent <jats:italic>ex vivo<\/jats:italic> effects upon acute EVR administration in healthy volunteers are rare. Moreover, immunosuppressive drugs are associated with neuroendocrine changes and psychological disturbances. It is largely unknown so far whether and to what extend EVR affects neuroendocrine functions, mood, and anxiety in healthy individuals. Thus, in the present study, we analyzed the effects of three different clinically applied EVR doses (1.5, 2.25, and 3\u00a0mg) orally administered 4 times in a 12\u2010hour cycle to healthy male volunteers on immunological, neuroendocrine, and psychological parameters. We observed that oral intake of medium (2.25\u00a0mg) and high doses (3\u00a0mg) of EVR efficiently suppressed T cell proliferation as well as IL\u201010 cytokine production in <jats:italic>ex vivo<\/jats:italic> mitogen\u2010stimulated peripheral blood mononuclear cell. Further, acute low (1.5\u00a0mg) and medium (2.25\u00a0mg) EVR administration increased state anxiety levels accompanied by significantly elevated noradrenaline (NA) concentrations. In contrast, high\u2010dose EVR significantly reduced plasma and saliva cortisol as well as NA levels and perceived state anxiety. Hence, these data confirm the acute immunosuppressive effects of the mTOR inhibitor EVR and provide evidence for EVR\u2010induced alterations in neuroendocrine parameters and behavior under physiological conditions in healthy volunteers.<\/jats:p>","DOI":"10.1111\/cts.12812","type":"journal-article","created":{"date-parts":[[2020,5,31]],"date-time":"2020-05-31T13:38:35Z","timestamp":1590932315000},"page":"1251-1259","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Dose\u2010Dependent Acute Effects of Everolimus Administration on Immunological, Neuroendocrine and Psychological Parameters in Healthy Men"],"prefix":"10.1111","volume":"13","author":[{"given":"Tina","family":"H\u00f6rbelt","sequence":"first","affiliation":[{"name":"Institute of Medical Psychology and Behavioral Immunobiology University Hospital Essen University of Duisburg\u2010Essen Essen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna Lena","family":"Kahl","sequence":"additional","affiliation":[{"name":"Institute of Medical Psychology and Behavioral Immunobiology University Hospital Essen University of Duisburg\u2010Essen Essen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frederike","family":"Kolbe","sequence":"additional","affiliation":[{"name":"Institute of Medical Psychology and Behavioral Immunobiology University Hospital Essen University of Duisburg\u2010Essen Essen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susann","family":"Hetze","sequence":"additional","affiliation":[{"name":"Clinic of Neurosurgery University Hospital Essen University of Duisburg\u2010Essen Essen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin","family":"Wilde","sequence":"additional","affiliation":[{"name":"Department of Nephrology University Hospital Essen University of Duisburg\u2010Essen Essen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oliver","family":"Witzke","sequence":"additional","affiliation":[{"name":"Department of Nephrology University Hospital Essen University of Duisburg\u2010Essen Essen Germany"},{"name":"Department of Infectious Diseases West German Centre of Infectious Diseases University Hospital Essen University of Duisburg\u2010Essen Essen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manfred","family":"Schedlowski","sequence":"additional","affiliation":[{"name":"Institute of Medical Psychology and Behavioral Immunobiology University Hospital Essen University of Duisburg\u2010Essen Essen Germany"},{"name":"Department of Clinical Neuroscience Osher Center for Integrative Medicine Karolinska Institutet Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,5,31]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20150149"},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1517\/17425255.4.6.807"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)00117-3"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2009.02832.x"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.2147\/TRRM.S12212"},{"key":"e_1_2_10_6_1","unstructured":"Novartis.Certican tablets: summary of product characteristics. <https:\/\/klinischeforschung.novartis.de\/dokumente\/fachinformationen\u2010certican\u2010tabletten\/>. Accessed April 15 2020."},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0000000000000260"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1592\/phco.22.3.154.33542"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1345\/aph.1A384"},{"key":"e_1_2_10_10_1","first-page":"11","article-title":"Bioavailability of everolimus administered as a single 5 mg tablet versus five 1 mg tablets: a randomized, open\u2010label, two\u2010way crossover study of healthy volunteers","volume":"7","author":"Thudium K.","year":"2015","journal-title":"Clin. Pharmacol."},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2008.02.015"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0156535"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-199707150-00007"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-199707150-00008"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0b013e3181bb43ec"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2018010009"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/TXD.0000000000000663"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfh322"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.transproceed.2009.08.050"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-198702000-00007"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-2277.2000.tb01004.x"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.psyneuen.2010.12.019"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40810-015-0004-x"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychires.2016.03.008"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2004.08.116"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2014.06.056"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/ijnp\/pyy017"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2014.75"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00033.2018"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2011.05.011"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1720548115"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2711"},{"key":"e_1_2_10_33_1","doi-asserted-by":"crossref","first-page":"5596","DOI":"10.4049\/jimmunol.158.12.5596","article-title":"Autocrine and paracrine regulation of human T cell IL\u201010 production","volume":"158","author":"Cohen S.","year":"1997","journal-title":"J. Immunol."},{"key":"e_1_2_10_34_1","doi-asserted-by":"crossref","first-page":"4167","DOI":"10.4049\/jimmunol.145.12.4167","article-title":"IL\u201010, a novel growth cofactor for mature and immature T cells","volume":"145","author":"MacNeil I.A.","year":"1990","journal-title":"J. Immunol."},{"key":"e_1_2_10_35_1","doi-asserted-by":"crossref","first-page":"4545","DOI":"10.4049\/jimmunol.151.9.4545","article-title":"Human IL\u201010 is a chemoattractant for CD8+ T lymphocytes and an inhibitor of IL\u20108\u2010induced CD4+ T lymphocyte migration","volume":"151","author":"Jinquan T.","year":"1993","journal-title":"J. Immunol."},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0000000000000630"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.4103\/2319-4170.110365"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2012.11.003"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2019.00511"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.287.5.622"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1177\/2045125312436574"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.2147\/NDT.S91311"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1097\/JGP.0b013e3181ec806c"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004872-199917060-00001"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncir.2018.00021"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40101-019-0193-2"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1593\/tlo.09277"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1677\/ERC-08-0269"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.4103\/2152-7806.77029"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-11-0270"}],"container-title":["Clinical and Translational Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.12812","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cts.12812","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.12812","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T09:29:20Z","timestamp":1693819760000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1111\/cts.12812"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,31]]},"references-count":50,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2020,11]]}},"alternative-id":["10.1111\/cts.12812"],"URL":"https:\/\/doi.org\/10.1111\/cts.12812","archive":["Portico"],"relation":{},"ISSN":["1752-8054","1752-8062"],"issn-type":[{"value":"1752-8054","type":"print"},{"value":"1752-8062","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,31]]},"assertion":[{"value":"2020-03-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-04-29","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-05-31","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}