title: Early treatment with chloroquine inhibits the immune response against Plasmodium yoelii infection in mice.
abstract: Chloroquine (CQ), a well-known anti-malarial drug, has long been used for the treatment of autoimmune diseases because of its profound immunomodulatory effects. However, whether this drug modifies anti-malaria immune response is still not clear. Here we studied the immunomodulatory role of CQ in a mouse model of malaria. DBA/2 mice were infected with Plasmodium yoelii (Py) parasite (intraperitoneal injection of parasitized erythrocytes) and divided into three groups. Two groups received single dose of CQ (gavage administration) at 6 hours after Py infection (post-6h) and 3 days after Py infection (post-3d), respectively. The third group received saline as control. The course of disease was monitored and the changes of immune response were investigated. It is shown that mice from the post-6h group took longer time to clear the parasites compared with those of the post-3d group. The activation of T helper cells, macrophages, and B cells was significantly suppressed in mice with post-6h CQ treatment as compared with control mice on day 3 and day 5 after infection. In contrast, no such changes were found in mice from the post-3d group. Dendritic cells (DCs) from the post-6h CQ treated mice were less mature as compared with those from control mice as well as those from the post-3d group. Taken together, our data suggest that treatment with CQ early in infection inhibits protective immune response against Py infection possibly via mechanisms involving the modulation of DC's function. Our finding provided important information for reasonable use of CQ in malaria chemotherapy.
authors.affiliation: Department of Immunology, College of Basic Medical Sciences, China Medical University.
authors.forename: Xiaosong
authors.initials: X
authors.lastname: Qin
authors.forename: Guang
authors.initials: G
authors.lastname: Chen
authors.forename: Yonghui
authors.initials: Y
authors.lastname: Feng
authors.forename: Xiaotong
authors.initials: X
authors.lastname: Zhu
authors.forename: Yunting
authors.initials: Y
authors.lastname: Du
authors.forename: Wei
authors.initials: W
authors.lastname: Pang
authors.forename: Zanmei
authors.initials: Z
authors.lastname: Qi
authors.forename: Yaming
authors.initials: Y
authors.lastname: Cao
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology / Q000627:therapeutic use; D002738:Chloroquine / Q000494:pharmacology / Q000627:therapeutic use*; D003713:Dendritic Cells / Q000187:drug effects; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D007111:Immunity, Cellular / Q000187:drug effects*; D056724:Immunity, Humoral / Q000187:drug effects*; D008288:Malaria / Q000188:drug therapy* / Q000276:immunology* / Q000469:parasitology; D008811:Mice, Inbred DBA; D010967:Plasmodium yoelii / Q000187:drug effects / Q000276:immunology*; D018418:Th2 Cells / Q000187:drug effects; D051217:Toll-Like Receptor 9 / Q000378:metabolism
chemical_list: D000962:Antimalarials; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; D002738:Chloroquine