Hypothalamic mechanisms of immunity.

The present article considers a synthetical analysis of the results reported by our laboratory in the last twenty years in the field of neuroimmunomodulation. The studies we discuss here continue a previous research activity, a synthesis of which has also been published in this journal (Baciu, 1988). In that paper, we reported data concerning the role of the hypothalamic tubero-mammillary area in triggering of the phagocytic and of the secondary immune specific response. Here, we present an analysis of experimental facts gathered after 1988, and also of some prior to that date, which were not included in the above-mentioned review. They regard localizations, attained with stereotactical methods, of hypothalamic areas involved in maintenance of basal phagocytosis and of its circadian rhythm, of the phagocytic and of the primary and secondary specific response. We attempted to re-analyze these data in an integrative view, and accomplish a coherent image of the hypothalamic mechanisms of the nonspecific and specific immune response. The conclusion we draw is that the nervous system may exert its modulatory action upon the immune response in several ways: i) subsequent to a direct hypothalamic stimulation (electrical or through bacteria or bacterial products) or to a cortico-hypothalamic stimulation; ii) depending on the nature, intensity, duration, and frequency of the appropriate stimulus, it may either enhance the immune response, via neural and humoral pathways, or depress it; iii) via the hypothalamus-pituitary-adrenal axis. Nervous triggering and enhancement of the immune response are essential, their occurrence in the initial stages ensuring its favorable course. The finding that repeated electroconvulsant shocks, employed for hypothalamus stimulation in dogs of different breed, age, weight, and individual history, are followed by extremely variable changes of the phagocytic activity raises the question on the individuality of the immune response.

Neutrophil adherence in rats submitted to light-dark alternance and to constant light.

A good amount of experimental data suggests the existence of a circadian control of the inflammatory process. It was shown that migration of neutrophils in chemotactic gradient, ingestion of particles, vascular permeability etc. are rhythmical circadian functions. Melatonin, the pineal hormone secreted during the darkness phase, has been shown to be involved in the control of inflammation. The present study aims to assess whether neutrophil adherence to nylon fibers exhibits circadian rhythmicity and also if its amplitude and/or chronostructure are altered in a constant light regimen. Wistar rats were submitted to either an artificial light-darkness 12/12 regimen (LD) or to constant light (LL), for 15 days. Adherence of the neutrophils in whole blood was assessed at 10:00, 16:00, 22:00, and 04:00 hrs. In LD. neutrophil adherence appears to be a rhythmic, biphasic function, with the acrophase at 10:00, a secondary peak at 22:00 and trough values in the late dark hours. Constant light induces a depression of the adherence ability by about 10%, except for the 04:00 hrs point, where the value in LL is higher than in LD. The fact that adherence and phagocytic activity do not oscillate in phase suggests that the physiological relevance of neutrophil adherence goes beyond that of a first stage of the phagocytic process.

Circadian phagocytic activity in rats under light-dark and constant light regimens.

The phagocytic function was proved to be a periodic, circadian process. Its acrophase appears to be differently timed in species with different activity type, occurring in the evening in diurnal species and at night in nocturnal ones. The main pineal hormone melatonin, whose secretion occurs strictly at dark, has been shown to play a role in the control of inflammation and to exert a certain stimulatory effect upon phagocytosis in vitro. The aim of the present study was to assess whether the phagocytic activity of neutrophils in the blood of rats exhibits a circadian rhythmicity similar to that of other nocturnal rodents (mice) and also if a constant light regimen alters its amplitude and/or chronostructure. Wistar rats were submitted to either an artificial light-dark 12/12 regimen (LD) or to constant light (LL), for 15 days. In vitro phagocytosis of the neutrophils in whole blood against E.coli was assessed at 10:00, 16:00, 22:00, and 04:00 hours. In LD, phagocytosis appears to be a rhythmical function, with statistically significant differences between the highest value at 04:00 hrs and the lowest at 10:00 hrs. Constant light induces a 30% depression of the phagocytic ability throughout the whole 24 hours cycle, without altering its oscillations. The darkness period appears to play the role of a synchronizer; in its absence the rhythm tends to free-run. It may be stated that rhythmical melatonin secretion is responsible only for maintenance of the phagocytic level, probably via the anterior hypothalamic area and thymus, while it cannot account directly for the nocturnal increase of phagocytosis.