CpG-C immunotherapeutic efficacy is jeopardized by ongoing exposure to stress: Potential implications for clinical use

Yael Goldfarb, Ben Levi, Liat Sorski, Dan Frenkel, Shamgar Ben-Eliyahu

Research output: Contribution to journalArticlepeer-review

Abstract

Bi-directional influences between stress hormones and immune responses have been repeatedly documented, however, in the clinical setting they are rarely considered when immunotherapeutic approaches are used or studied in patients. As some immunotherapeutic treatments have shown great potential in animal models but have had limited success in patients, we hypothesize that ongoing psychological and physiological stress responses in patients, which do not characterize the setting of animal studies, contribute to this discrepancy. In the current study we examined the interaction between ongoing water stress and CpG-C immunotherapy to determine whether stress that precedes immunotherapy can modulate the efficacy of CpG-C immunostimulation. C57BL/6 mice were exposed to water stress or served as controls. Two hours following the commencement of the stress protocol animals were injected with CpG-C, non-CpG, or PBS, and sacrificed 1, 4 or 12h thereafter. We found that in CpG-C-treated animals stress eliminated the elevation of plasma IL-12, and synergistically elevated corticosterone levels. Furthermore, stress markedly reduced the total number of myeloid (33D1+), plasmacytoid (mPDCA-1+) and plasmacytoid-derived (33D1+mPDCA-1+) dendritic cells in CpG-C-treated animals, as well as the numbers of these cell sub-types expressing CD11b, CD80 and CD69. These changes were more dramatic in the blood than in the spleen. Overall, these findings indicate that under no-stress conditions CpG-C induces a robust immune response, which is significantly diminished when immunostimulation is attempted during ongoing stress. If these findings hold in humans, potential prophylactic treatments should be found to limit the deleterious effects of ongoing stress on the efficacy of immunotherapy.

Original languageEnglish
Pages (from-to)67-76
Number of pages10
JournalBrain, Behavior, and Immunity
Volume25
Issue number1
DOIs
StatePublished - Jan 2011

Keywords

  • Corticosterone
  • CpG-C
  • Dendritic cells
  • IL-12
  • Stress

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