title: In vivo and in vitro immunosuppressive effects of benzo[k]fluoranthene in female Balb/c mice.
abstract: Although polycyclic aromatic hydrocarbons (PAHs) have been known to suppress immune responses, few studies have addressed the immunotoxicity of benzo[k]fluoranthene (B[k]F). In this study, we investigated the immunosuppression by B[k]F, both in vivo and in vitro, in female BALB/c mice. To assess the effects of B[k]F on humoral immunity as splenic antibody response to sheep red blood cells (SRBCs), B[k]F was given a single dose or once daily for 7 consecutive days po with 30, 60, and 120 micromol/kg. B[k]F reduced the number of antibody-forming cells (AFCs) in a dose-dependent manner. Subacute treatment with B[k]F caused weight increases in liver and decreases in spleen and thymus. The number of AFCs was dramatically decreased by B[k]F in a dose-dependent manner. In a subsequent study, mice were subacutely exposed to the same doses of B[k]F without an immunization with SRBCs, followed by splenic and thymic lymphocyte phenotypings using a flow cytometry and ex vivo mitogen-stimulated proliferation. B[k]F-exposed mice exhibited reduced splenic and thymic cellularity, decreased numbers of total T cells, CD4(+) cells, and CD8(+) cells in spleen, and immature CD4(+)CD8(+) cells, CD4(+)CD8(-) cells, and CD8(+)CD4(-) cells in thymus. The number of CD4(+) IL-2(+) cells was reduced by about 11%, 31%, and 53% following exposure of mice to 30, 60, and 120 micromol/kg of B[k]F, respectively. In the ex vivo lymphocyte proliferation assay, B[k]F inhibited splenocyte proliferation by LPS and Con A. In the in vitro mitogen-stimulated proliferation by untreated splenic suspensions, B[k]F only suppressed splenocyte proliferation to LPS. These results suggested that B[k]F-induced immunosuppression might be mediated, at least in part, through the IL-2 production, and caused by mechanisms associated with metabolic processes.
authors.affiliation: College of Pharmacy, Yeungnam University, Kyungsan, South Korea. taecheon@yumail.ac.kr
authors.forename: Tae Won
authors.initials: TW
authors.lastname: Jeon
authors.forename: Chun Hua
authors.initials: CH
authors.lastname: Jin
authors.forename: Sang Kyu
authors.initials: SK
authors.lastname: Lee
authors.forename: Dong Wook
authors.initials: DW
authors.lastname: Lee
authors.forename: Sun Hee
authors.initials: SH
authors.lastname: Hyun
authors.forename: Ghee Hwan
authors.initials: GH
authors.lastname: Kim
authors.forename: In Hye
authors.initials: IH
authors.lastname: Jun
authors.forename: Byung Mu
authors.initials: BM
authors.lastname: Lee
authors.forename: Young Na
authors.initials: YN
authors.lastname: Yum
authors.forename: Jun Kyou
authors.initials: JK
authors.lastname: Kim
authors.forename: Ok Hee
authors.initials: OH
authors.lastname: Kim
authors.forename: Tae Cheon
authors.initials: TC
authors.lastname: Jeong
mesh_terms: D000818:Animals; D000921:Antibody-Producing Cells / Q000187:drug effects / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002274:Carcinogens, Environmental / Q000633:toxicity; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D005449:Fluorenes / Q000633:toxicity*; D007166:Immunosuppressive Agents / Q000633:toxicity*; D007376:Interleukin-2 / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D012756:Sheep; D013154:Spleen / Q000166:cytology / Q000187:drug effects*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects*
chemical_list: D002274:Carcinogens, Environmental; D005449:Fluorenes; D007166:Immunosuppressive Agents; D007376:Interleukin-2; C022921:benzo(k)fluoranthene