Circadian variation in serum cortisol and circulating neutrophils are markers for circadian variation of bone marrow proliferation in cancer patients.

Abstract

Serum cortisol, circulating white blood cells and DNA cell cycle distribution in bone marrow cells were measured during daytime (11.00) and at midnight (24.00) over single 24-hour periods in 15 cancer patients. The neutrophils and fraction of bone marrow cells in S-phase showed the same circadian variation as cortisol with higher values in daytime as compared to midnight in 11 patients with a normal cortisol rhythm (p < 0.05). The lymphocytes, eosinophils and basophils all had significantly higher values at midnight as compared to daytime. There were significant correlations between cortisol and neutrophils, lymphocytes, eosinophils and basophils. The correlation between neutrophils and fractions of bone marrow cells in S-phase and S + G2/M-phase were highly significant (r = 0.74, p = 0.0001 and r = 0.72, p = 0.0001, respectively). In 8 of 13 patients (61.5%) without bone marrow infiltration both cortisol and neutrophils showed identical circadian variation as bone marrow cells in S-phase and S + G2/M-phase. Furthermore, for the total series a significant correlation between S-phase, cortisol and neutrophils was found by multiple regression analysis (p < 0.0001). These findings strengthen the possibility of using the circadian variation in cortisol and neutrophils as marker rhythms for circadian variation in bone marrow proliferation, thus allowing optimization of cytotoxic therapy and individualization of chronotherapy.