Expression of lymphocyte subsets after exercise and dexamethasone in high and low stress responders.

PURPOSE: Recent work indicates that among the normal population, persons can be classified as low (LR) or high (HR) stress responders based on hypothalamic-pituitary-adrenal (HPA) axis responses to high-intensity exercise. We studied whether differential activation of the HPA axis affected cytokine production and expression of selected lymphocyte subsets in HR and LR in response to high-intensity exercise after placebo and dexamethasone (DEX; 4 mg). METHODS: Healthy HR (N = 12) and LR (N = 10) underwent two exercise tests at 90% of VO2max, 8 h after placebo or DEX. Expression of lymphocyte surface markers (CD3+, CD4+, CD8+, CD56+), adhesion molecule markers (intercellular adhesion molecule-1/ICAM-1: CD54+ and L-selectin: CD62L+), and concentrations of plasma interleukin 6 (IL-6) were examined before and after exercise. RESULTS: Baseline percentages of CD8+ and CD56+ cells were significantly higher, and concentrations of IL-6 and percentages of CD4+ cells were significantly lower in HR as compared with LR. The percentage of CD54+ and CD62L+ cells was not significantly different in HR and LR. DEX significantly reduced the percentage of CD3+ and CD4+ and increased the percentage of CD8+ and CD56+ subsets; the percent of cells expressing CD54+ increased, whereas CD62L+ decreased. Exercise-induced changes in the percentage of lymphocyte subsets were similar to those induced by DEX. CONCLUSION: In summary, HR and LR have different baseline patterns of IL-6 and lymphocyte subsets, which may reflect differential sensitivity to endogenous glucocorticoids. However, exogenous glucocorticoids induced similar patterns of lymphocyte expression in HR and LR.

Lymphocyte subpopulation expression in women: effect of exercise and circadian rhythm.

It is well established that exercise affects immune responses in men, but little information is available for women. Whether exercise-induced immune responses are affected by circadian rhythm has not been determined. This study examined lymphocyte responses of women to exercise in the morning (AM) and evening (PM). Lymphocytes expressing markers for T, B, and natural killer (NK) cells were identified by FACScan in blood samples collected before (baseline), immediately after, and 40 min after exercise (recovery). Absolute counts of all lymphocyte subpopulations increased immediately after exercise, but at recovery values were below baseline counts. Circadian variations were noted in absolute counts for total T, helper/inducer T cells, and B cells. Although these counts were significantly higher in the PM, the magnitude of the immune response to exercise was the same in the AM and PM. In contrast, natural killer cells, both the relative counts and the magnitude of immune response were higher in the AM. Thus, it appears that despite differences in baseline cell counts the overall exercise-induced response in most lymphocyte subpopulations is similar in the AM and PM.

Lymphocyte subset responses to exercise and glucocorticoid suppression in healthy men.

It is well established that in vivo changes in ratios of lymphocyte phenotype subsets is altered by glucocorticoid administration. To determine whether the lymphocyte response would be further affected by strenuous exercise, since glucocorticoids are released during exercise, 14 physically fit men were randomly given placebo (P), 4 mg of dexamethasone (DEX), or 100 mg of hydrocortisone (HCO) 4 h before high-intensity treadmill running. Blood was drawn pre- and immediately post-exercise; lymphocyte subsets (CD3, CD4, CD8, CD19, and CD56) were determined by flow cytometry. Pre-exercise CD3 and CD4 percentages were lower, whereas CD8 and CD56 were higher with DEX and HCO as compared to P. Exercise induced a lymphocytosis after all treatments, but subsets did not change proportionally. With P, DEX, and HCO, the magnitudes of change were comparable: CD3 and CD4 decreased and CD8 and CD56 increased. Notably, for all treatments exercise induced in approximately 2-fold increase in the percentage of cells expressing CD56 (natural killer cells). Thus, a single oral dose of DEX or HCO did not alter the direction or magnitude of immediate post-exercise changes in lymphocyte subset expression. Whether glucocorticoid pretreatment influences lymphocyte responses during recovery from strenuous exercise remains to be determined.

Release of hypothalamic corticotropin-releasing hormone and arginine-vasopressin by interleukin 1 beta and alpha MSH: studies in rats with different susceptibility to inflammatory disease.

The susceptibility of Lewis rats is related to blunted hypothalamic-pituitary-adrenal (HPA) axis responsiveness to a variety of inflammatory and neuroendocrine stimuli. In contrast resistance to inflammatory disease of histocompatible Fischer rats is associated with their intact HPA axis responses to the same stimuli. We have examined the contribution of IL-1 beta to in vitro corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) release from hypothalamic explants derived from LEW/N and F344/N rats. The same animal model has been used to investigate the regulatory effect of alpha MSH, an immunosuppressive neurohormone, on IL-1 beta stimulated CRH and AVP secretion. CRH basal release in both strains was similar. However, LEW/N hypothalamic AVP basal secretion was significantly elevated. CRH relative response of LEW/N hypothalamic explants to IL-1 beta stimulation was lower compared to Fischer, which is consistent with their hyporesponsiveness to inflammatory mediators. AVP secretion however, was significantly decreased in hypothalamic explants from both strains after 40 min exposure to IL-1 beta. alpha MSH suppressed basal CRH and AVP release in both LEW/N and F344/N rats and prevented IL-1 beta stimulated CRH secretion in these strains. AVP was further diminished in F344/N explants following incubation with alpha MSH + IL-1 beta, while LEW/N level was significantly elevated. However, AVP levels remained significantly below baseline in explants from both strains after final incubation with IL-1 beta. Although our findings indicate a modulatory action of alpha MSH in HPA axis regulation in vitro, the physiological importance of this phenomenon in Lewis and Fischer rats requires further investigation.