Melatonin:
A Synchronizing Signal for the Immune System by Daniel P. Cardinali, Luis I. Brusco, Laura Selgas and
Ana I. Esquifino
Introduction
Biological time measurement in adult and fetal mammals is critically
dependent upon the melatonin signal (Arendt, 1995; Reiter, 1995;
Cardinali et al., 1997b). The mechanisms sensitive to melatonin,
which mediates the clock message, may reside in the brain, in
the biological clock itself, i.e., the suprachiasmatic nuclei
(SCN). There are also data indicating that melatonin receptors
are universally distributed throughout in the body and can convey
circadian-meaningful information to every cell in the organism,
playing the role of an "internal Zeitgeber" (Armstrong,
1991).
Among melatonin's versatile functions, immunomodulation has
emerged as a major effect of the hormone in vertebrates. The
identification of melatonin involvement in immunomodulation
was a direct consequence of studies on melatonin and pineal
gland participation in regulation of tumor growth, an area in
which the late Prof. Derek Gupta made substantial contributions.
Indeed, the melatonin rhythm seems to be a very important efferent
pathway of the SCN to impose synchronicity to the immune system.
The brain, as well as the peripheral immune cells, may
be able to encode an accumulated memory of melatonin signals,
thereby defining time intervals at the 24-hour cycle and the
annual scale.
