C. Lopes et al., CIRCADIAN-RHYTHM IN EXPERIMENTAL GRANULOMATOUS INFLAMMATION IS MODULATED BY MELATONIN, Journal of pineal research, 23(2), 1997, pp. 72-78
Biological rhythms are detected in a variety of physiological and path
ological conditions in man and animals, such as rheumatoid arthritis a
nd asthma. Here we describe a circadian rhythm in experimental infecti
ous and non-infectious granuloma, After 30 days of BCG (Bacillus Calme
tte-Guerin) or nystatin inoculation in the left hind foot of C57B1/6 m
ice, there is an oscillation with a period of approximately 24 hr in t
he variation of paw thickness, indicating a circadian rhythm. The acro
phase occurred during the light phase, between 9:00 and 13:00 hr, whil
e the nadir occurred in the dark phase, between 21:00 and 01:00 hr. Th
e vascular permeability around the granulomatous lesions was higher at
12:00 hr than at 24:00 hr. This is in agreement with the observation
that the thickness of a paw with granulomatous lesion is larger during
the light phase,This rhythmic variation was eliminated by either pine
alectomy or superior cervical ganglionectomy, which greatly reduce mel
atonin levels in the blood. Nocturnal replacement of melatonin in pine
alectomized mice led to the re-establishment of the circadian rhythm.
Thus, the rhythm of the granulomatous lesion is due to the rhythmic me
latonin release by the pineal gland. This approach opens new questions
regarding the modulation of chronic inflammation in inflammatory dise
ases that present rhythmic symptoms throughout the day.