Toll-like receptor 4 mediates chronic restraint stress-induced immune suppression

Yi Zhang, Michael Woodruff, Ying Zhang, Junying Miao, Gregory Hanley, Charles Stuart, Xiao Zeng, Savita Prabhakar, Jonathan Moorman, Baoxiang Zhao, Deling Yin

Research output: Contribution to journalArticlepeer-review

41 Scopus citations


Stress, either physical or psychological, can have a dramatic impact on the immune system. Little progress, however, has been made in understanding stress-induced immune suppression. We report here that mice subjected to chronic 12-hour daily physical restraint for two days significantly increased the expression of Toll-like receptor 4 (TLR4). Interestingly, TLR4-deficient mice are resistant to stress-induced lymphocyte reduction. In addition, restraint stress caused dramatic decrease in T help 1 (Th1) cytokine IFN-γ and IL-2 levels but increase in Th2 cytokine IL-4 in wild type mice. Moreover, the restraint stress significantly inhibits changes of Th1 and Th2 cytokines in TLR4-deficient mice compared with the wild type mice. Therefore, stress modulates the immune system through a TLR4-dependent mechanism.

Original languageEnglish (US)
Pages (from-to)115-122
Number of pages8
JournalJournal of Neuroimmunology
Issue number1-2
StatePublished - Feb 2008
Externally publishedYes


  • Chronic stress
  • Mice
  • Microarray
  • TLR4
  • Th1 and Th2 cytokines

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology


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