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. However, the factors that regulate these rhythms are not well understood. In the current study, we examined the diurnal variations of peripheral blood cells (white blood cells, neutrophils, lymphocytes), granulocyte-macrophage-colony stimulating factor (GM-CSF), and melatonin levels, and considered the role of melatonin on these rhythms in healthy volunteers and in patients with early breast cancer. Fourteen premenopausal patients with early stage breast cancer (T2, N1 tumors) and 10 premenopausal healthy volunteers were included in the study. Blood samples were taken every 4 hr for a period of 24 hr. Peripheral blood cells were counted by automated analyser and also from peripheral blood films. GM-CSF levels were measured by ELISA and melatonin levels by radioimmunoassay (RIA). Serum melatonin, cortisol, and GM-CSF levels, and peripheral blood cell counts showed significant circadian rhythms in healthy volunteers. Except for GM-CSF, these circadian rhythms were found not to be suppressed in early breast cancer patients. While there were significant correlations of serum GM-CSF and cortisol levels with peripheral blood cell counts in healthy volunteers, only lymphocyte counts were found to be significantly correlated with serum GM-CSF and cortisol levels in patients with breast cancer. Serum melatonin levels were found to be significantly correlated with lymphocyte counts in both groups. Our results suggest that peripheral blood cells show significant circadian rhythms in both healthy 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 peripheral blood cell counts.