In vivo and in vitro immunosuppressive effects of benzo[k]fluoranthene in female Balb/c mice.
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.
Jeon
Tae Won
TW
College of Pharmacy, Yeungnam University, Kyungsan, South Korea. taecheon@yumail.ac.kr
Jin
Chun Hua
CH
Lee
Sang Kyu
SK
Lee
Dong Wook
DW
Hyun
Sun Hee
SH
Kim
Ghee Hwan
GH
Jun
In Hye
IH
Lee
Byung Mu
BM
Yum
Young Na
YN
Kim
Jun Kyou
JK
Kim
Ok Hee
OH
Jeong
Tae Cheon
TC
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*
D002274:Carcinogens, Environmental; D005449:Fluorenes; D007166:Immunosuppressive Agents; D007376:Interleukin-2; C022921:benzo(k)fluoranthene