The role of granulocyte-macrophage-colony stimulating factor, cortisol, and melatonin in the regulation of the circadian rhythms of peripheral blood cells in healthy volunteers and patients with breast cancer

The circulating blood cells show highly reproducible circadian rhythms. How ever, the factors that regulate these rhythms are not well understood. In t he current study, we examined the diurnal variations of peripheral blood ce lls (white blood cells, neutrophils, lymphocytes), granulocyte-macrophage-c olony stimulating factor (GM-CSF), and melatonin levels, and considered the role of melatonin on these rhythms in healthy volunteers and in patients w ith early breast cancer. Fourteen premenopausal patients with early stage b reast cancer (T2, NI tumors) and 10 premenopausal healthy volunteers were i ncluded in the study. Blood samples were taken every 4 hr for a period of 2 4 hr. Peripheral blood cells were counted by automated analyser and also fr om peripheral blood films. GM-CSF levels were measured by ELISA and melaton in levels by radioimmunoassay (RIA). Serum melatonin, cortisol, and GM-CSF levels, and peripheral blood cell counts showed significant circadian rhyth ms in healthy volunteers. Except for GM-CSF, these circadian rhythms were f ound not to be suppressed in early breast cancer patients. While there were significant correlations of serum GM-CSF and cortisol levels with peripher al blood cell counts in healthy volunteers, only lymphocyte counts were fou nd to be significantly correlated with serum GM-CSF and cortisol levels in patients with breast cancer. Serum melatonin levels were found to be signif icantly correlated with lymphocyte counts in both groups. Our results sugge st that peripheral blood cells show significant circadian rhythms in both h ealthy volunteers and in patients with stage II (T2, N1) breast cancer, and GM-CSF, cortisol, and melatonin may have a role in the regulation of perip heral blood cell counts.