Modulatory Factors of Circadian Phagocytic Activity

Abstract

Basal phagocytosis of neutrophils, a crucial component of non-specific immunity, is an eminently circadian parameter. In mice and rats, rates of phagocytosis peak in the second half of the dark span. A lipopolysaccharide-induced phagocytic response challenged in this period appears the most significant in amplitude and duration. Neonatal administration in rats of the neurotoxic agent monosodium glutamate, which induces massive destruction of the arcuate nucleus, suppresses the phagocytic response and moderately inhibits basal phagocytosis. Physiological phagocytosis in vivo appears to depend on the presence of the nocturnal melatonin surge. Functional pinealectomy, achieved in rats by a 2-week exposure to constant light, lowered the average circadian level of phagocytosis, damped the characteristic rhythm of neutrophil adherence, and decreased the neutrophil count and the amplitude of its circadian oscillation. In an in vivo study, adult rats were given alcohol intraperitoneally (0.1 mL ethanol/kg body weight, 1:10 in saline solution), alone or co-administered with melatonin (1 mg/kg body weight), for 16 days, once a day at 20:00 h. Alcohol-treated animals displayed a drastically depressed and flattened phagocytic curve, a marked decline of the adherence ability, and a reduction of the mean circadian neutrophil and lymphocyte count. Addition of melatonin significantly increased circadian values of phagocytosis, restored adherence, and prevented the numeric depletion of lymphocytes induced by alcohol. In correlation with other experimental evidence, our data speak for a physiological role of melatonin in upkeep of neutrophil phagocytosis and hint towards the existence of several pineal-hypothalamic pathways regulating different components of phagocytosis in vivo.