title: Pyrethroid insecticides influence the signal transduction in T helper lymphocytes from atopic and nonatopic subjects.
abstract: OBJECTIVE
  Pyrethroids are claimed to have a low human toxicity with some neuro- and immunotoxicity. The objective of this study was to investigate the immunotoxicological properties of six commercially used pyrethroids, including natural pyrethrum and synergist piperonyl-butoxide (PBO).
  
  
  METHODS
  PHA-stimulated cultures of T-helper lymphocytes and blood basophil incubates from nonatopic and atopic patients (IgE > 1000 IU) provided cytokine and histamine determination. Western blot analysis was used for the measurement of Th2-specific signal transducer and activator of transcription-6 (STAT6). Pyrethroids and xenobiotics were added 4 h post-plating.
  
  
  RESULTS
  We demonstrated that interferon-gamma (IFN-gamma) production and expression was correlated with lymphocyte proliferation, however, interleukin-4 (IL-4) was down-regulated at the end of the 3 day culture. Atopics showed significantly higher IL-4 activity than nonatopics. Pyrethroids inhibited IFN-gamma and IL-4 in both groups at around 10(-5) M. Only fenvalerate and S-bioallethrin combined with 10-fold PBO in the atopic-enriched blood basophil incubates caused a weak but significant increase in histamine release. Histamine acted bidirectionally on STAT6, but pyrethroids inhibited the intracellular Th2-specific STAT6 more effectively in atopics than in nonatopics.
  
  
  CONCLUSIONS
  It can be suggested that pyrethroids inhibit signal transduction in human lymphocytes ex vivo, and do not act via lymphocyte-influencing histamine release.
authors.affiliation: Institut für Umwelt und Gesundheit, University of Applied Sciences FH Fulda, Marquardstrasse 35, 36039 Fulda, Germany. friedhelm.diel@t-online.de
authors.forename: F
authors.initials: F
authors.lastname: Diel
authors.forename: B
authors.initials: B
authors.lastname: Horr
authors.forename: H
authors.initials: H
authors.lastname: Borck
authors.forename: T
authors.initials: T
authors.lastname: Irman-Florjanc
mesh_terms: D000328:Adult; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006632:Histamine / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000503:physiopathology*; D007306:Insecticides / Q000494:pharmacology*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D019055:No-Observed-Adverse-Effect Level; D011722:Pyrethrins / Q000494:pharmacology*; D012313:RNA / Q000737:chemistry / Q000302:isolation & purification; D015398:Signal Transduction / Q000187:drug effects*; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects*; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: D016207:Cytokines; D007306:Insecticides; D011722:Pyrethrins; D013778:Tetrazolium Salts; D013844:Thiazoles; D015847:Interleukin-4; D012313:RNA; D006632:Histamine; D007371:Interferon-gamma; C022616:thiazolyl blue