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The aim of this study consisted in underlining the concentrations' evolution in time of two cytokines: IL-1 beta and IFN-gamma, as well as that of RIL-2 (soluble receptor for IL-2), in healthy volunteers. Under normal physiological conditions, these molecules are secreted in small amounts, according to a sequential chronology. Thus, 25 blood samples were carried out from each of the four subjects included in the study, one every 20 minutes, during 8 hours. Concentrations were determined with the ELISA method. Spectral analysis was carried out using the Frequencies Spectrum method (Fourier Transform of a temporal series). This method allows a rhythm search over a milited number of values, in a short interval of time, provided having enough samples. Important variabilities have been observed between all subjects sera, particularly for IL-1 beta (Range (mean +/- SD): 132 +/- 34.6 pg/ml to 250 +/- 17.5 pg/ml, one subject had low values: 2.34 +/- 0.53 pg/ml) and RIL-2 (Range: 677 +/- 175 pg/ml to 1,187 +/- 46.2 pg/ml). Furthermore, ultradian serum variations, characterized by the relation ((Cmax-Cmin)/Cmax) x 100, have been assessed for each subject and each molecule: IL-1 beta (Range: 18.9 to 92.2%), IFN-gamma (Range: 66.3 to 74.2%) and RIL-2 (Range: 11.6 to 86.3%); they might be the manifestation of a periodicity; this hypothesis has been confirmed by the spectral analysis. Thus, the concentrations' variation with time showed a periodicity (Range: 80 mn to 240 mn, the most frequent period was 160 mn (2 h 40 mn)).

The circadian rhythms in plasma ACTH, TSH, LH and PRL were explored in sighted or blind, spayed and estrogen-implanted rats. A marked endogenous circadian rhythmicity was shown to persist in the blind animals for the 4 endocrine rhythms. The endogenous rhythms also kept very close reciprocal phase relationship as in the synchronized state, and they were peaking almost simultaneously, after 60 d. of free-running. Finally the endogenous hormonal rhythm maintained their usual phase relationships with the endogenous activity rhythm, so that the circadian phase of increased hormonal secretion coincided with the circadian resting phase of the sleep/wake rhythm. These results are discussed in the light of the alternate theory of one vs multiple but phase-locked circadian pacemakers driving endocrine and behavioral circadian rhythms.

The effects of bilateral destruction of suprachiasmatic nuclei (SCN) on the temporal patterns of plasma concentrations in ACTH and corticosterone (sequential blood samples from an aortic cannula, at 4 h intervals over 48 h) and of general activity (stabilimeter recordings) were studied in female rats under constant illumination (LL : 10 lx). Under this arrhythmic environment, the SCN lesions induced a syndrome similar to that previously described in a photoperiodic environment (12 L-12 D). This SCN syndrome included : 1) blockade of the ACTH rhythm at baseline levels ; 2) maintained fluctuations of corticosterone, with either circadian or ultradian profiles ; 3) persistent rhythmicity of general activity, with a circadian periodicity in addition to ultradian periods. The persistence of a circadian rhythmicity in the SCN syndrome under arrhythmic environmental conditions, clearly argues in favour of the occurrence of endogenous components of the circadian pacemaker outside the SCN.