Immunomodulatory effects of in vitro stress hormones on FoxP3, Th1/Th2 cytokine and costimulatory molecule mRNA expression in human peripheral blood mononuclear cells.
BACKGROUND
Stress influences immune function through mechanisms including an impact on regulatory elements. We have previously demonstrated that glucocorticoids (GCs) and catecholamines can influence immunomodulation including changes in Th1/Th2 cytokine production. These immunoregulatory imbalances are associated with elevated cortisol in vivo and in the presence of GCs in vitro.


METHODS
We examined the effects of dexamethasone (DEX) and epinephrine (EPI) on the balance of regulatory T cells (Tregs), Th1/Th2 cytokine gene expression by peripheral blood mononuclear cells (PBMCs) from 16 normal subjects after 24-hour and 11-day cultures with tetanus toxoid. We wished to determine whether the immunomodulatory effects of stress hormones involved differences in costimulatory signal pathways including CD28, CTLA-4 (CD152), and CD80/86.


RESULTS
Our results revealed that FoxP3 mRNA expression (representing Tregs) was decreased in PBMCs cultured with DEX relative to the control within 24 h (short term). DEX decreased the Th1/Th2 cytokine mRNA balance after 11 days (long term). CD28 and CD80 mRNA were decreased in short-term incubation with DEX whereas the effect of inhibition by DEX on CTLA-4 mRNA was detected only in long-term cultures.


CONCLUSIONS
These results suggest that the Treg (FoxP3 mRNA) and CD28/CD80 costimulatory signal pathway may be a target of stress hormones in acute stress while the CTLA-4/CD80-86 pathway may be more susceptible in chronic stress.
Xiang
Lianbin
L
Laboratory of Behavioral Immunology Research, Division of Clinical Immunology and Allergy, Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39126-4505, USA.
Marshall
Gailen D
GD
D000293:Adolescent; D000328:Adult; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology*; D004837:Epinephrine / Q000494:pharmacology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis*; D013312:Stress, Physiological / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D055815:Young Adult
D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger; D003907:Dexamethasone; D004837:Epinephrine