Circadian Variations in Human Peripheral Blood on Days With and Without Bone Marrow Sampling and Relation to Bone Marrow Cell Proliferation

Abstract

Fifteen bone marrow (BM) and venous blood circadian profiles were obtained from 13 diurnallyactive, healthy men sampled every 4-5 h for 24 h. Peripheral blood (PB) was also sampled in subsets of 5 men either for 24 h immediately preceding the BM procedure or 5-6 months afterwards. Cortisol and white and red cell parameters were determined in PB. BM cell cycle distribution was investigated in parallel by flow cytometry for S-phase DNA of total mononuclear cells and subpopulations of erythroid and myeloid precursor cells. On a group basis, significant circadian rhythms were found in PB variables commonly referred to as "marker" rhythms (cortisol, total white cells [WBC], neutrophils [N], lymphocytes [L]), with acrophases less than 2 h apart between the control day prior to and during BM sampling. Thus, major, but relatively short-lasting physiological stress, like BM aspirations or blood sampling itself, although repeated several times over 24 h, seemed to have minor influence on these rhythms on days of the BM procedure. When comparing the times of highest or lowest values in PB with times of highest or lowest values in BM, several temporal relationships were found. Among other associations, timing of lowest values in WBC, N and L or highest values in cortisol was significantly predictive of highest values in myeloid cells occurring in the following 12 h, whereas highest values in erythroid cells occurred significantly more often in the 12 h interval beginning 4 h after the time of lowest values in WBC, L and N. The stability in the circadian rhythms of the PB variables suggests that information obtained on one day can be used to guide procedures on the next, such as BM myelotoxic chronotherapy or BM harvesting.

Chemotherapy delivery time affects treatment outcomes of female patients with diffuse large B cell lymphoma

“…Although we suggest a biologic mechanism for hematologic toxicity based on the larger fluctuation of hemogram in females compared to males, a more detailed mechanism for this phenomenon should be delineated in future studies. In fact, previous studies also revealed circadian fluctuation of both hemogram and DNA synthetic activity of bone marrow (37,(50)(51)(52). These studies consistently showed peak immune cell count in the afternoon or evening as in our findings (Figure 5).…”

Circadian variations do not have a major impact on serum levels of soluble (s) L-selectin (CD63L), s-intercellular adhesion molecule 1 (sICAM-1/CD54) and thrombopoietin in healthy individuals

“…total leukocyte and granulocyte counts demonstrates that the investigated persons showed an expected circadian variation in hematopoietic parameters and thus should be regarded as rep-DI S CU SSI ON resentative for healthy individuals [12 ]. Our results then demonstrated that serum levels of Recent reports suggest that analysis of serum levels of sl-selectin, sICAM-1 and Tpo may be all three molecules showed only minimal variations during a 24-h period.…”

“…However, several immunocompetent and hematopoietic therapy-induced thrombocytopenia induced relatively large alterations in the serum levels of all cells show circadian functional variations [11][12][13][14], and the possible use of serum levels of three mediators compared with the minor variations during a normal 24-h period. Even the sl-selectin, sICAM-1 or Tpo in clinical practice therefore requires a clari cation of whether the early drop in serum Tpo level for one individual (see Fig.…”

“…The concentrations in venous blood samples (Vacutainer sample collection tubes with EDTA-cytokine levels can show such variations [11][12][13], and these biological rhythms may also in uence anticoagulant) of total leukocytes, granulocytes and platelets were also determined at 07.00 and systemic levels of soluble adhesion molecules derived from immunocompetent/hematopoietic 19.00 h. These samples were collected during the same venipuncture and immediately following cells as well as the levels of cytokines involved in the regulation of hematopoiesis. The release the samples for serum preparation.…”

“…Samples were stored at room temperature and analyzed of sl-selectin and sICAM-1 by immunocompetent cells may in addition be modulated by the within 14 h on a Technicon H2 analyzer (Bayer, Leverkusen, Germany). circadian variations in serum cortisone [12], a hormone with well-known immunomodulatory eVects [12][13][14]. To further evaluate the possible use of sl-selectin, sICAM-1 and Tpo in RE SULTS clinical medicine, it is therefore necessary to clarify whether their serum levels show circadian…”