The mechanisms of stress-related immune alterations have not been fully elu
cidated. Cell-mediated immune responses as well as antibody and certain cyt
okines are reported as being suppressed during times of high stress. Howeve
r, the role of suppression vs dysregulation has not been established in hum
an stress models. The effect of exam stress on regulatory cytokines in 16 h
ealthy medical students was assessed by measuring type-1 (IFN-gamma) and ty
pe-2 (IL-10) cytokines from 72-h PHA/PMA-stimulated PBMC 4 weeks before and
48 h after exams. Results demonstrated decreased IFN-gamma accompanied by
increased IL-10 during exam stress that resulted in a decreased IFN-gamma:I
L-10 ratio. There was a significant correlation between the cytokine respon
se to PHA/PMA and number and subjective adjustment to daily hassles. Additi
onally, students who reported greater levels of loneliness also reported gr
eater numbers of and poorer subjective adjustment to hassles. The differenc
es were consistent in both males and females but did not correlate with AM
cortisol levels. Additionally, when individuals were grouped into high vs l
ow preexam hassle levels, the type-1/type-2 shift in the IFN-gamma:IL-10 ra
tio occurred in the low hassles group only. These data suggest that psychol
ogically stressful situations shift type-1/type-2 cytokine balance toward t
ype-2 and result in an immune dysregulation rather than overall immunosuppr
ession. This may partially explain the increased incidence of type-2-mediat
ed conditions such as increased viral infections, latent viral expression,
allergic/asthmatic reactions, and autoimmunity reported during periods of h
igh stress. (C) 1998 Academic Press.