Circadian variations in antigen-specific proliferation of human T lymphocytes and correlation to cortisol production

Cortisol is a well-known immunosuppressant when used therapeutically. The present investigation was set out to study if diurnal variations in endogenous cortisol production are reflected by changes in proliferative responses of human lymphocytes to either a mitogen (phytohemagglutinin-A, PHA) or an antigen (tetanus toxoid, TT) stimulus. The study included eight healthy volunteers. Blood was withdrawn at 0200, 0600, 1000, and 1800h for preparation of lymphocytes and determination of cortisol in plasma. Isolated cells were incubated without (baseline activity) or with inclusion of either 1 micrograms PHA or 10 micrograms TT. Proliferation was measured by labelling with 3H-thymidine for 16 h of culture. The cortisol plasma levels exhibited the well known diurnal variations with highest concentrations at 1000h and lowest levels at 0200h. Baseline activity or PHA stimulated cell proliferation did not show significant diurnal fluctuations. The response to TT, however, decreased by 38% between 0600 and 1000h (p = .01). Correlation analyses revealed that the reduction of the proliferative responses to TT correlated significantly (p < .05) with increases in cortisol plasma levels. It was concluded that diurnal fluctuations in the production of endogenous cortisol might be relevant for daytime dependent variations in immune responsiveness.