title: Immunotoxicity induced by acute subtoxic doses of paraquat herbicide: implication of shifting cytokine gene expression toward T-helper (T(H))-17 phenotype.
abstract: Paraquat (PQ) is a free radical-inducing agent commonly used as an herbicide. This study assesses the acute immunotoxicity of PQ in BALB/c mice and examines its effect on cytokine gene expression profile. It was found that single subtoxic oral doses of 2, 4, and 20 mg/kg significantly inhibited the in vitro mitogen-induced proliferation in both T and B cells. Also, such acute doses have resulted in significant reduction of the IgM plaque-forming cells counts. The impact of PQ on the cytokine gene expression of in vitro PHA-activated splenocytes was assessed at 2.0 and 0.006 μg/mL. The concentrations used in vitro represent the lowest in vivo dose given in this study and FAO-WHO set PQ acceptable daily intake (ADI) dose, respectively. Interestingly, the RT²-PCR array for common cytokines' expression demonstrated that PQ had markedly elevated the mRNA expression of several proinflammatory cytokines at both concentrations. More importantly, at concentrations equivalent to ADI, PQ had caused a marked up-regulation of IL-17 cytokine family including IL-17B, C, E, and F. Also, PQ has up-regulated mRNA expression of the T(H)-17-promoting cytokines IL-9 and -21. Together, these results show that PQ at higher concentrations can deplete immune functions, but at lower concentrations, it has potential to alter immune responses toward the proinflammatory profiles as that of T(H)-17. Such a T cell helper profile has been implicated in the development and the pathophysiology of several autoimmune and allergic diseases. Thus, considering that maximum residue levels (MRLs) of PQ set by FAO and WHO for certain food and animal feed crops range between 0.005 and 10.0 mg/kg, our findings stress the importance of applying strict regulation on the use of PQ as an herbicide.
authors.affiliation: Department of Biological Sciences, Faculty of Science, University of Jordan, Amman 11942, Jordan. hassuneh@yahoo.com
authors.forename: Mona R
authors.initials: MR
authors.lastname: Hassuneh
authors.forename: Maysaa' A
authors.initials: MA
authors.lastname: Albini
authors.forename: Wamidh H
authors.initials: WH
authors.lastname: Talib
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000235:genetics*; D005260:Female; D006403:Hematologic Tests; D006540:Herbicides / Q000008:administration & dosage / Q000276:immunology* / Q000633:toxicity; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D010269:Paraquat / Q000008:administration & dosage / Q000276:immunology* / Q000633:toxicity; D012333:RNA, Messenger / Q000235:genetics; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016207:Cytokines; D006540:Herbicides; D012333:RNA, Messenger; D010269:Paraquat