title: Aflatoxin B1 modulates the expression of phenotypic markers and cytokines by splenic lymphocytes of male F344 rats.
abstract: Aflatoxin B1 (AFB1) is immunotoxic to animals and a suspected immunosuppressant in humans. In this study, we investigated the effects of AFB1 on splenic lymphocyte phenotypes and the inflammatory cytokine expression in male F344 rats. Exposure of animals to AFB1 [5-75 µg kg(-1) body weight (BW)] for 1 week showed dose-dependent decreases in the percentage of splenic CD8(+) T cells and CD3(-) CD8a(+) NK cells. A general inhibition of the expression of interleukin (IL)-4 and interferon (IFN)-γ by CD4(+) T cells, IL-4 and IFN-γ by CD8a(+) cells, and tumor necrosis factor (TNF)-α expression by natural killer (NK) cells was also found; however, no concurrent histological changes in spleen tissue were present, suggesting acute immunosuppression without overt toxicity. Five-week exposure with AFB1 significantly increased the percentages of CD3(+) and CD8(+) T cells, especially at low doses (≤ 25 µg kg(-1)). AFB1 treatment significantly decreased the anti-inflammatory cytokine IL-4 expression by CD4(+) T cells and significantly increased the pro-inflammatory cytokine IFN-γ expression by CD4(+) T cells and TNF-α expression by NK cells. These results indicated that repeated AFB1 exposure promotes inflammatory responses by regulating cytokine expression. Our data provides novel insights into the mechanisms by which AFB1 exposure differentially modulates the cell-mediated immune responses and suggests the involvement of an inflammatory response upon repeated exposure.
authors.affiliation: Department of Environmental Health Science, University of Georgia, Athens, GA 30602, USA.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Qian
authors.forename: Lili
authors.initials: L
authors.lastname: Tang
authors.forename: Xia
authors.initials: X
authors.lastname: Guo
authors.forename: Franklin
authors.initials: F
authors.lastname: Wang
authors.forename: Michael E
authors.initials: ME
authors.lastname: Massey
authors.forename: Jianjia
authors.initials: J
authors.lastname: Su
authors.forename: Tai L
authors.initials: TL
authors.lastname: Guo
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Williams
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Phillips
authors.forename: Jia-Sheng
authors.initials: JS
authors.lastname: Wang
mesh_terms: D000284:Administration, Oral; D016604:Aflatoxin B1 / Q000633:toxicity*; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D005434:Flow Cytometry; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology; D008297:Male; D010641:Phenotype; D051381:Rats; D011916:Rats, Inbred F344; D013154:Spleen / Q000187:drug effects* / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology
chemical_list: D016207:Cytokines; D004785:Environmental Pollutants; D016604:Aflatoxin B1
keywords: aflatoxin B1; cytokine; lymphocyte; spleen; surface marker expression