Impact of stress, gender and menstrual cycle on immune system: Possible role of nitric oxide

Stress is a factor found to be involved in the etiology of many diseases. Gender and menstrual cycle phases are other factors affecting the predisposition of individuals for certain diseases. Results from animal and human studies suggest that the distribution of immune system cells may change at different phases of the menstrual cycle. Acute mental stress in humans alters immune variables, too. The increase in the number of natural killer (NK) cells is the most consistent finding among the immune variables, though there are controversies for the other lymphocyte groups. Nitric oxide (NO) as an immune mediator has an unsettled role whether it causes the redistribution of the immune cells, or is an end product of lymphocyte activation. This study was planned to investigate the effect of mental stress on lymphocyte subtypes and the role of NO, for men and women at different phases of the cycle. For this purpose, healthy men (n = 10) and women (n = 10), during the follicular and luteal phases underwent Stroop colour-word interference and cold pressor tests. The immune system responses before and after the tests were determined by cell counts with the flowcytometer. Menstrual cycle phase was ascertained by plasma estrogen and progesterone measurements. Stress response was evaluated by blood pressure (BP) and heart rate (HR) measurements throughout the tests and plasma cortisol and urinary metanephrine and vanillylmandelic acid (VMA) measurements before and after the tests. Plasma and urinary NO determinations were performed before and after the test was completed. All the results were analysed with the appropriate statistical methods. The luteal phase differed from the other groups due to the presence of suppressed immune response to acute stress, including decreased CD4/CD8 ratio and NK cell percentage. On the other hand, acute stress caused a shift from cellular to humoral immunity in men. As indicated by these results, individual reaction towards stress is affected by gender and menstrual cycle phase. NO appears to be a possible effector molecule for these differences.