Chronopharmacologic Effects of Recombinant Human Granulocyte Colony-Stimulating Factor (rhG-CSF) on Hematopoiesis in Mice

Li, Xiaomei; Lévi, Francis

doi:10.1076/brhm.30.3.339.3049

Biological Rhythm Research

1999

DOI: 10.1076/brhm.30.3.339.3049

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Chronopharmacologic Effects of Recombinant Human Granulocyte Colony-Stimulating Factor (rhG-CSF) on Hematopoiesis in Mice

Xiaomei Li¹,

Francis Lévi²

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In-vitro circadian rhythm of murine bone marrow progenitor production

Bourin

Ledain

Beau

et al. 2002

Chronobiology International

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Hematopoietic processes display 24h rhythms both in rodents and in human beings. We hypothesized these rhythms to be in part generated by a circadian oscillator within the bone marrow. The ability of murine bone marrow granulo-monocytic (GM) precursors to form colonies following colony-stimulating factor (rm GM-CSF) exposure was investigated in liquid culture samples obtained every 3 h for a span of up to 198 h. The CFU-GM count varied rhythmically over the first 4 d of culture, with a reproducible maximum in the early morning hours, similar to that observed in vivo. These experiments provide the first evidence that bone marrow progenitors sustain in vitro circadian rhythmicity, and they demonstrate the presence of a circadian time-keeping system within these cells. The results support the potential usefulness of bone marrow cultures for investigating chronopharmacologic effects of anticancer drugs and cytokines on this target system.

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In-vitro circadian rhythm of murine bone marrow progenitor production

Bourin

Ledain

Beau

et al. 2002

Chronobiology International

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Circadian Rhythms: Mechanisms and Therapeutic Implications

Lévi

Schibler

2007

Annu. Rev. Pharmacol. Toxicol.

566

494

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The mammalian circadian system is organized in a hierarchical manner in that a central pacemaker in the suprachiasmatic nucleus (SCN) of the brain's hypothalamus synchronizes cellular circadian oscillators in most peripheral body cells. Fasting-feeding cycles accompanying rest-activity rhythms are the major timing cues in the synchronization of many, if not most, peripheral clocks, suggesting that the temporal coordination of metabolism and proliferation is a major task of the mammalian timing system. The inactivation of noxious food components by hepatic, intestinal, and renal detoxification systems is among the metabolic processes regulated in a circadian manner, with the understanding of the involved clock output pathways emerging. The rhythmic control of xenobiotic detoxification provides the molecular basis for the dosing time-dependence of drug toxicities and efficacy. This knowledge can in turn be used in improving or designing chronotherapeutics for the patients who suffer from many of the major human diseases.

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Chronopharmacologic Effects of Recombinant Human Granulocyte Colony-Stimulating Factor (rhG-CSF) on Hematopoiesis in Mice

Cited by 2 publications

References 0 publications

In-vitro circadian rhythm of murine bone marrow progenitor production

In-vitro circadian rhythm of murine bone marrow progenitor production

Circadian Rhythms: Mechanisms and Therapeutic Implications

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