Evaluation of immunosuppression induced by metronidazole in Balb/c mice and human peripheral blood lymphocytes Mohammad Fararjeh a,1 , Mohammad K. Mohammad b, ⁎ , Yasser Bustanji b , Hatim AlKhatib b , Shtaywy Abdalla a a Department of Biological Sciences, faculty of science, The University of Jordan, Amman 11942, Jordan b Faculty of Pharmacy, The University of Jordan, Amman 11942, Jordan Received 6 August 2007; received in revised form 11 October 2007; accepted 16 October 2007 Abstract The immunomodulatory effect of metronidazole (MTZ), a nitroimidazole drug used as an antiprotozoal and antibacterial agent, was investigated using Balb/c mice and human peripheral blood lymphocytes. For in vivo studies, mice were divided into six groups, six animals per group, group I received vehicle alone while the other groups (II–VI) received intraperitoneal injections of MTZ (14, 28, 42, 57, and 114 mg/kg) respectively. For in vitro studies different concentrations of MTZ (5, 10, 50, and 200 μg/ml) were used. MTZ showed a significant decrease in the percentage of circulating neutrophils and monocytes and an increase in the percentage of circulating lymphocytes. The relative weights of spleen as well as the relative body weight gain also decreased. Detectable changes were seen in the histology of spleen and thymus. Splenic plaque-forming cells (PFC), hemagglutination (HA) titer to sheep red blood cells (SRBC), spleenocytes and human peripheral blood lymphocytes proliferation (MLR) were markedly suppressed by MTZ treatment as compared to control group. MTZ also induced a significant decrease in delayed-type hypersensitivity (DTH) reaction, phagocytic activity (assessed by phagocytic capacity and phagocytic index) as well as TNF-α secretion by peritoneal macrophages. These observations indicate that MTZ significantly induced immunosuppression in mice and in human peripheral blood lymphocytes. © 2007 Elsevier B.V. All rights reserved. KEYWORDS Metronidazole; Immunotoxicity; Human peripheral blood lymphocytes; Balb/c mice 1. Introduction Nitroheterocyclic chemicals have a wide variety of applications, ranging from food preservatives to antibio- tics. 5-nitroimidazoles are a well-established group of antiprotozoan and antibacterial agents. They have a ⁎ Corresponding author. Faculty of Pharmacy, The University of Jordan, Amman 11942, Jordan. Tel.: +962 6 5355000x23336; fax: +962 6 5339 649. E-mail address: mkmohammad@ju.edu.jo (M.K. Mohammad). 1 Present address: Jerusalem Consulting Medical laboratories, Yajouz, Jordan. 1567-5769/$ - see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.intimp.2007.10.018 www.elsevier.com/locate/intimp International Immunopharmacology (2008) 8, 341–350