{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T16:14:23Z","timestamp":1770740063532,"version":"3.49.0"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2014,3,1]],"date-time":"2014-03-01T00:00:00Z","timestamp":1393632000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Deanship of Academic Research, Hashemite University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>The immunomodulatory effects of clozapine (CLZ), antipsychotic drug, were investigated in vivo using female Balb\/c mice. The main aim of this study was to evaluate the immunomodulatory effects of CLZ, antipsychotic drug, following daily intraperitoneal injection to female Balb\/c mice over a period of 21 days.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Mice were divided into five groups, eight animals per group. Group I, served as a control group, received only the vehicle. Groups II\u2013V received a daily intraperitoneal dose of CLZ (1, 5, 10 and 20 mg\/kg, respectively) over a period of 21 days.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Key findings<\/jats:title>\n                  <jats:p>CLZ has shown a significant decrease in the animal body weight, and it showed a significant decrease in the percentage of circulating neutrophils and lymphocytes while circulating monocytes were increased. The immunotoxicity has been also assessed by evaluating spleen cellularity, humoral immune response to a foreign antigen using sheep red blood cells and delayed-type hypersensitivity reaction. The results showed a marked suppression in these responses in CLZ-treated mice compared with the control group. Detectable changes have also been noticed in the histology of the footpad tissue and spleen.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Results showed significant immunomuodulatory effects of CLZ when used in Balb\/c mice.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1111\/jphp.12150","type":"journal-article","created":{"date-parts":[[2013,12,11]],"date-time":"2013-12-11T01:56:38Z","timestamp":1386726998000},"page":"378-386","source":"Crossref","is-referenced-by-count":7,"title":["Assessment of possible immunotoxicity of the antipsychotic drug clozapine"],"prefix":"10.1093","volume":"66","author":[{"given":"Yaseen","family":"Abdelrahman","sequence":"first","affiliation":[{"name":"Department of Medical Laboratory Sciences, Faculty of Allied Health Sciences, The Hashemite University , Zarqa,","place":["Jordan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad","family":"Fararjeh","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Sciences, Faculty of Allied Health Sciences, The Hashemite University , Zarqa,","place":["Jordan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wesam","family":"Abdel-Razeq","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Sciences, Faculty of Allied Health Sciences, The Hashemite University , Zarqa,","place":["Jordan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad K","family":"Mohammad","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, The University of Jordan , Amman,","place":["Jordan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasser","family":"Bustanji","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, The University of Jordan , Amman,","place":["Jordan"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2014,3,1]]},"reference":[{"key":"2024103109153508900_jphp12150-cit-0001","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.toxlet.2011.04.027","article-title":"Developmental immunotoxicity of di-n-octyltin dichloride (DOTC) in an extended one-generation reproductive toxicity study","volume":"204","author":"Tonk","year":"2011","journal-title":"Toxicol Lett"},{"key":"2024103109153508900_jphp12150-cit-0002","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1080\/15476910490438342","article-title":"Suppression of immune function and susceptibility to infections in humans: association of immune function with clinical disease","volume":"1","author":"Luebke","year":"2004","journal-title":"J Immunotoxicol"},{"key":"2024103109153508900_jphp12150-cit-0003","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/15476910802656440","article-title":"Summary of a workshop on nonclinical and clinical immunotoxicity assessment of immunomodulatory drugs","volume":"6","author":"Piccotti","year":"2009","journal-title":"J Immunotoxicol"},{"key":"2024103109153508900_jphp12150-cit-0004","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/j.jconrel.2004.01.005","article-title":"Preparation, characterization and in vitro release kinetics of clozapine solid lipid nanoparticles","volume":"95","author":"Venkateswarlu","year":"2004","journal-title":"J Control Release"},{"key":"2024103109153508900_jphp12150-cit-0005","doi-asserted-by":"crossref","first-page":"4548","DOI":"10.1016\/j.bmcl.2006.06.034","article-title":"Modification of the clozapine structure by parallel synthesis","volume":"16","author":"Su","year":"2006","journal-title":"Bioorg Med Chem Lett"},{"key":"2024103109153508900_jphp12150-cit-0006","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1093\/schbul\/sbl068","article-title":"Clozapine underutilization and discontinuation in African Americans due to leucopenia","volume":"33","author":"Kelly","year":"2007","journal-title":"Schizophr Bull"},{"key":"2024103109153508900_jphp12150-cit-0007","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.taap.2006.01.008","article-title":"Increased FasL expression correlates with apoptotic changes in granulocytes cultured with oxidized clozapine","volume":"214","author":"Husain","year":"2006","journal-title":"Toxicol Appl Pharmacol"},{"key":"2024103109153508900_jphp12150-cit-0008","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1016\/S0009-9236(99)70072-X","article-title":"The cytotoxicity of clozapine metabolites: implications for predicting clozapine-induced agranulocytosis","volume":"65","author":"Tschen","year":"1999","journal-title":"Clin Pharmacol Ther"},{"key":"2024103109153508900_jphp12150-cit-0009","first-page":"96","article-title":"Agranulocytosis monitoring with clozapine patients: to follow guidelines or to attempt therapeutic controversies?","volume":"49","author":"Chandrasekaran","year":"2008","journal-title":"Singapore Med J"},{"key":"2024103109153508900_jphp12150-cit-0010","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1136\/pgmj.2004.031161","article-title":"Clozapine, agranulocytosis, and benign ethnic neutropenia","volume":"81","author":"Rajagopal","year":"2005","journal-title":"Postgrad Med J"},{"key":"2024103109153508900_jphp12150-cit-0011","doi-asserted-by":"crossref","first-page":"e23","DOI":"10.1016\/j.forsciint.2011.07.032","article-title":"Clozapine \u2013 a dangerous drug in a clozapine-naive subject","volume":"214","author":"Stanworth","year":"2012","journal-title":"Forensic Sci Int"},{"key":"2024103109153508900_jphp12150-cit-0012","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1002\/hup.1181","article-title":"Haematological toxicity of clozapine and some other drugs used in psychiatry","volume":"26","author":"Nooijen","year":"2011","journal-title":"Hum Psychopharmacol"},{"key":"2024103109153508900_jphp12150-cit-0013","doi-asserted-by":"crossref","first-page":"26","DOI":"10.3371\/CSRP.5.1.4","article-title":"Impact of complete blood count sampling time change on white blood cell and absolute neutrophil count values in clozapine recipients","volume":"5","author":"McKee","year":"2011","journal-title":"Clin Schizophr Relat Psychoses"},{"key":"2024103109153508900_jphp12150-cit-0014","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1016\/j.tiv.2008.08.002","article-title":"Clozapine-induced hepatotoxicity in rat hepatocytes by gel entrapment and monolayer culture","volume":"22","author":"Lu","year":"2008","journal-title":"Toxicol In Vitro"},{"key":"2024103109153508900_jphp12150-cit-0015","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1517\/17425255.2.2.249","article-title":"Methods of evaluating immunotoxicity","volume":"2","author":"Descotes","year":"2006","journal-title":"Expert Opin Drug Metab Toxicol"},{"issue":"Suppl. 6","key":"2024103109153508900_jphp12150-cit-0016","first-page":"877","article-title":"Approaches to detecting immunotoxic effects of environmental contaminants in humans","volume":"109","author":"Tryphonas","year":"2001","journal-title":"Environ Health Perspect"},{"key":"2024103109153508900_jphp12150-cit-0017","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.toxlet.2003.12.025","article-title":"Sensitivity and predictivity in immunotoxicity testing: immune endpoints and disease resistance","volume":"149","author":"Germolec","year":"2004","journal-title":"Toxicol Lett"},{"key":"2024103109153508900_jphp12150-cit-0018","doi-asserted-by":"crossref","first-page":"127","DOI":"10.2165\/00002018-200528020-00004","article-title":"Immunotoxicology: role in the safety assessment of drugs","volume":"28","author":"Descotes","year":"2005","journal-title":"Drug Saf"},{"key":"2024103109153508900_jphp12150-cit-0019","first-page":"207","article-title":"The Mighty Mouse: the impact of rodents on advances in biomedical research","volume":"110","author":"Bryda","year":"2013","journal-title":"Mo Med"},{"key":"2024103109153508900_jphp12150-cit-0020","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1007\/s11064-011-0670-4","article-title":"Evaluation of the antipsychotic potential of Panax quinquefolium in ketamine induced experimental psychosis model in mice","volume":"37","author":"Chatterjee","year":"2012","journal-title":"Neurochem Res"},{"key":"2024103109153508900_jphp12150-cit-0021","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1016\/j.fct.2010.03.036","article-title":"Immunotoxicity of paraquat after subacute exposure to mice","volume":"48","author":"Riahi","year":"2010","journal-title":"Food Chem Toxicol"},{"key":"2024103109153508900_jphp12150-cit-0022","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.intimp.2007.10.018","article-title":"Evaluation of immunosuppression induced by metronidazole in Balb\/c mice and human peripheral blood lymphocytes","volume":"8","author":"Fararjeh","year":"2008","journal-title":"Int Immunopharmacol"},{"key":"2024103109153508900_jphp12150-cit-0023","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/S1567-5769(02)00292-8","article-title":"Immunomodulatory effects of fenugreek (Trigonella foenum graecum L.) extract in mice","volume":"3","author":"Bin-Hafeez","year":"2003","journal-title":"Int Immunopharmacol"},{"key":"2024103109153508900_jphp12150-cit-0024","doi-asserted-by":"crossref","first-page":"3435","DOI":"10.1128\/AAC.49.8.3435-3441.2005","article-title":"Establishment of a superficial skin infection model in mice by using Staphylococcus aureus and Streptococcus pyogenes","volume":"49","author":"Kugelberg","year":"2005","journal-title":"Antimicrob Agents Chemother"},{"key":"2024103109153508900_jphp12150-cit-0025","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.tox.2006.09.003","article-title":"In vitro tests to evaluate immunotoxicity: a preliminary study","volume":"229","author":"Carfi","year":"2007","journal-title":"Toxicology"},{"key":"2024103109153508900_jphp12150-cit-0026","doi-asserted-by":"crossref","first-page":"255","DOI":"10.3109\/1547691X.2010.509848","article-title":"Present and future of in vitro immunotoxicology in drug development","volume":"7","author":"Galbiati","year":"2010","journal-title":"J Immunotoxicol"},{"key":"2024103109153508900_jphp12150-cit-0027","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.2165\/11530020-000000000-00000","article-title":"Adverse endocrine and metabolic effects of psychotropic drugs: selective clinical review","volume":"23","author":"Bhuvaneswar","year":"2009","journal-title":"CNS Drugs"},{"key":"2024103109153508900_jphp12150-cit-0028","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/S0920-9964(03)00190-7","article-title":"Clozapine's effects on body weight and resting metabolic rate: a case series","volume":"66","author":"Procyshyn","year":"2004","journal-title":"Schizophr Res"},{"key":"2024103109153508900_jphp12150-cit-0029","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1038\/oby.2006.6","article-title":"Hormonal and metabolic effects of olanzapine and clozapine related to body weight in rodents","volume":"14","author":"Albaugh","year":"2006","journal-title":"Obesity (Silver Spring)"},{"key":"2024103109153508900_jphp12150-cit-0030","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.2217\/14622416.9.8.1101","article-title":"Clozapine-induced agranulocytosis and its genetic determinants","volume":"9","author":"Opgen-Rhein","year":"2008","journal-title":"Pharmacogenomics"},{"key":"2024103109153508900_jphp12150-cit-0031","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.imlet.2011.06.011","article-title":"Antipsychotic drugs suppress the AKT\/NF-kappaB pathway and regulate the differentiation of T-cell subsets","volume":"140","author":"Chen","year":"2011","journal-title":"Immunol Lett"},{"key":"2024103109153508900_jphp12150-cit-0032","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.pnpbp.2008.12.006","article-title":"Atypical antipsychotics suppress production of proinflammatory cytokines and up-regulate interleukin-10 in lipopolysaccharide-treated mice","volume":"33","author":"Sugino","year":"2009","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry"},{"key":"2024103109153508900_jphp12150-cit-0033","first-page":"39","article-title":"[A change of immune profile of patients with schizophrenia during treatment]","volume":"104","author":"Koliaskina","year":"2004","journal-title":"Zh Nevrol Psikhiatr Im S S Korsakova"},{"key":"2024103109153508900_jphp12150-cit-0034","first-page":"737","article-title":"Effect of some antipsychotic drugs on immunoreactivity in C57BL\/6 mice","volume":"54","author":"Basta-Kaim","year":"2002","journal-title":"Pol J Pharmacol"},{"key":"2024103109153508900_jphp12150-cit-0035","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/978-1-60761-401-2_13","article-title":"The delayed type hypersensitivity assay using protein and xenogeneic cell antigens","volume":"598","author":"Dietert","year":"2010","journal-title":"Methods Mol Biol"},{"key":"2024103109153508900_jphp12150-cit-0036","doi-asserted-by":"crossref","first-page":"708","DOI":"10.7164\/antibiotics.47.708","article-title":"Suppressive effect of cyclosporin A on delayed-type hypersensitivity to syngeneic testicular cells","volume":"47","author":"Sakamoto","year":"1994","journal-title":"J Antibiot (Tokyo)"}],"container-title":["Journal of Pharmacy and Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjphp.12150","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjphp.12150","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jpp\/article-pdf\/66\/3\/378\/60251849\/jphp12150.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jpp\/article-pdf\/66\/3\/378\/60251849\/jphp12150.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,31]],"date-time":"2024-10-31T09:19:56Z","timestamp":1730366396000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jpp\/article\/66\/3\/378\/6127979"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,3,1]]},"references-count":36,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2014,3,1]]},"published-print":{"date-parts":[[2014,3,1]]}},"URL":"https:\/\/doi.org\/10.1111\/jphp.12150","relation":{},"ISSN":["2042-7158","0022-3573"],"issn-type":[{"value":"2042-7158","type":"electronic"},{"value":"0022-3573","type":"print"}],"subject":[],"published-other":{"date-parts":[[2014,3]]},"published":{"date-parts":[[2014,3,1]]}}}