Toll-like receptor 4 mediates chronic restraint stress-induced immune suppression.
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-gamma 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.
Zhang
Yi
Y
Departments of Internal Medicine, James Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, United States.
Woodruff
Michael
M
Zhang
Ying
Y
Miao
Junying
J
Hanley
Gregory
G
Stuart
Charles
C
Zeng
Xiao
X
Prabhakar
Savita
S
Moorman
Jonathan
J
Zhao
Baoxiang
B
Yin
Deling
D
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation; D007165:Immunosuppression Therapy; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D018121:Receptors, Cytokine / Q000096:biosynthesis / Q000235:genetics; D012149:Restraint, Physical / Q000009:adverse effects*; D013312:Stress, Physiological / Q000209:etiology / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D016207:Cytokines; D018121:Receptors, Cytokine; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4