Immunotoxicity of aflatoxin B1: impairment of the cell-mediated response to vaccine antigen and modulation of cytokine expression.
Aflatoxin B1 (AFB1), a mycotoxin produced by Aspergillus flavus or A. parasiticus, is a frequent contaminant of food and feed. This toxin is hepatotoxic and immunotoxic. The present study analyzed in pigs the influence of AFB1 on humoral and cellular responses, and investigated whether the immunomodulation observed is produced through interference with cytokine expression. For 28 days, pigs were fed a control diet or a diet contaminated with 385, 867 or 1807 microg pure AFB1/kg feed. At days 4 and 15, pigs were vaccinated with ovalbumin. AFB1 exposure, confirmed by an observed dose-response in blood aflatoxin-albumin adduct, had no major effect on humoral immunity as measured by plasma concentrations of total IgA, IgG and IgM and of anti-ovalbumin IgG. Toxin exposure did not impair the mitogenic response of lymphocytes but delayed and decreased their specific proliferation in response to the vaccine antigen, suggesting impaired lymphocyte activation in pigs exposed to AFB1. The expression level of pro-inflammatory (TNF-alpha, IL-1beta, IL-6, IFN-gamma) and regulatory (IL-10) cytokines was assessed by real-time PCR in spleen. A significant up-regulation of all 5 cytokines was observed in spleen from pigs exposed to the highest dose of AFB1. In pigs exposed to the medium dose, IL-6 expression was increased and a trend towards increased IFN-gamma and IL-10 was observed. In addition we demonstrate that IL-6 impaired in vitro the antigenic- but not the mitogenic-induced proliferation of lymphocytes from control pigs vaccinated with ovalbumin. These results indicate that AFB1 dietary exposure decreases cell-mediated immunity while inducing an inflammatory response. These impairments in the immune response could participate in failure of vaccination protocols and increased susceptibility to infections described in pigs exposed to AFB1.
Meissonnier
Guylaine M
GM
Laboratoire de Pharmacologie-Toxicologie UR66, INRA, F-31931 Toulouse, France.
Pinton
Philippe
P
Laffitte
Joëlle
J
Cossalter
Anne-Marie
AM
Gong
Yun Yun
YY
Wild
Christopher P
CP
Bertin
Gérard
G
Galtier
Pierre
P
Oswald
Isabelle P
IP
D016604:Aflatoxin B1 / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D016207:Cytokines / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D007111:Immunity, Cellular / Q000187:drug effects*; D007132:Immunoglobulin Isotypes / Q000187:drug effects / Q000378:metabolism; D000922:Immunotoxins / Q000008:administration & dosage / Q000633:toxicity*; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008934:Mitogens / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology; D016133:Polymerase Chain Reaction; D013154:Spleen / Q000378:metabolism; D013552:Swine; D014612:Vaccines / Q000276:immunology
D016207:Cytokines; D007132:Immunoglobulin Isotypes; D000922:Immunotoxins; D008934:Mitogens; D014612:Vaccines; D010047:Ovalbumin; D016604:Aflatoxin B1