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Pyrethroid insecticides influence the signal transduction in T helper lymphocytes from atopic and nonatopic subjects
Diel, Friedhelm ...
Objective and design: 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, inc(uding natural pyrethrum and synergist piperonyl-butoxide (PBO). Material and 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. Onlyfenvalerate 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 thc intracellular Th2-spceific STAT6 more effectively inatopics than in nonatopics. Conclusion: lt can be suggested that pyrethroidsinhibit signal transduction in human lymphocytes ex vivo, and do not act via lymphocyte-influencing histamine release.
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