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Nine healthy young men were studied under strict conditions for 48h. The subjects were selected after a clinical examination and exploration of their rest-activity rhythm by actometry. The circadian rhythms of cortisol (peak at 8 AM) and melatonin (peak at 4 AM) were confirmed. The interleukin 15 (IL-15) was detected in the plasma samples with an Elisa kit (R&D System®), but no reproducible variation could be observed during day 1 and day 2. In conclusion, in the conditions of our study, no rhythm was observed for IL-15. Our population will be completed with the inclusion of 6 additional subjects. These results will be specified. [Copyright &y& Elsevier]

Abstract: Influence of stress on immunity and pathogenesis relates to corticotropic axis: hypothalamus–hypophysis-surrenals (HHS). Its over-stimulation due to traumas during early childhood or before birth seems to generate brain abnormalities such as reduction of hippocampus volume. More typical of adult age, hypothalamus-pineal gland axis (HP), responsible for melatonin production, may be impaired because of chronic stress, mainly through sleep disturbances or addictive behaviours. Old age has been reported to produce same impairments. Circadian cycle of melatonin is closely related to immune functions and its disturbance seems to induce, among populations undergoing frequent changes of life rhythm, a significant raise of cancer incidence: night shift workers, air pilots… Stress then seems enable to increase cancer risk through its negative impact on HHS and HP axis and therefore on immunity. Immunotherapy, which was an interesting solution considering this, has not yield yet expected results. Upstream, other ways have been successfully investigated in prospective randomised trials, such as psychotherapeutic treatments, with positive effects on cellular immunity and survival. The ability to condition immune responses in animals allows thinking that hypnotherapy could also be used along with standard treatments. [Copyright &y& Elsevier]

Abstract: Melatonin is a small lipophile molecule, essentially secreted by pineal gland. The synthesis of this hormone shows a circadian pattern with a peak around 2–3 hours am. Many melatonin receptors are found in the body, which explains its multiple functions as biological rhythms resynchronisation, sleep induction, vasoregulation and even immunomodulation. Many experiments realised in this field have permit to discover differents interactions between melatonin and the immune system, and especially the link which exists between melatonin and the fight against cancer via the immune system. Phase II studies reported a decrease of thrombocytopenia, an increase of some cytokins rate and an increase of objective responses in cancer patients. In order to confirm these results and to lead further research, we propose to realise a phase II randomised study melatonin versus placebo in metastatic breast cancer patients after two lines of treatment. [Copyright &y& Elsevier]