There is still uncertainty whether extremely low frequency electromagnetic fields (ELF‐EMF) can induce health effects like immunomodulation. Despite evidence obtained in vitro, an unambiguous association has not yet been established in vivo. Here, mice were exposed to ELF‐EMF for 1, 4, and 24 h/day in a short‐term (1 week) and long‐term (15 weeks) set‐up to investigate whole body effects on the level of stress regulation and immune response. ELF‐EMF signal contained multiple frequencies (20–5000 Hz) and a magnetic flux density of 10 μT. After exposure, blood was analyzed for leukocyte numbers (short‐term and long‐term) and adrenocorticotropic hormone concentration (short‐term only). Furthermore, in the short‐term experiment, stress‐related parameters, corticotropin‐releasing hormone, proopiomelanocortin (POMC) and CYP11A1 gene‐expression, respectively, were determined in the hypothalamic paraventricular nucleus, pituitary, and adrenal glands. In the short‐term but not long‐term experiment, leukocyte counts were significantly higher in the 24 h‐exposed group compared with controls, mainly represented by increased neutrophils and CD4 ± lymphocytes. POMC expression and plasma adrenocorticotropic hormone were significantly lower compared with unexposed control mice. In conclusion, short‐term ELF‐EMF exposure may affect hypothalamic‐pituitary‐adrenal axis activation in mice. Changes in stress hormone release may explain changes in circulating leukocyte numbers and composition. Bioelectromagnetics. 37:433–443, 2016. © 2016 The Authors. Bioelectromagnetics Published by Wiley Periodicals, Inc.
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