Biology Reference
In-Depth Information
Further examination of melatonin activity on circadian rhythmicity of cell pro-
liferation in submaxillary lymph nodes and spleen at the clinical phase of arthritis
was conducted in young and old Sprague-Dawley rats
[137]
. Pineal melatonin con-
tent was measured, as well as the efficacy of melatonin treatment to recover modi-
fied circadian rhythmicity of submaxillary lymph node and splenic ODC and TH
activities and of lymph node
3
H-acetylcholine synthesis. After 17 daily injections
of 10 or 100 g of melatonin in the evening, the treatment restored the inflamma-
tory response in old rats (assessed plethysmographically in hind paws) to the level
found in young animals. In young rats, an inflammation-promoting effect of 100-g
melatonin was demonstrated. As a consequence of the immune reaction, submaxil-
lary lymph node and splenic lymph cell proliferation augmented significantly, with
acrophases of 24-hour rhythms in the afternoon for lymph nodes and in the morning
for spleen. Mesor and amplitude of ODC rhythm were lowest in old rats, although
melatonin injection generally augmented its amplitude. Lymph node and splenic
TH activity attained maximal values at early night, while maxima in lymph node
3
H-acetylcholine synthesis occurred in the afternoon. Amplitude and mesor of these
rhythms were lowest in old rats, an effect generally counteracted by melatonin treat-
ment. The results are compatible with an age-dependent, significant depression of
pineal melatonin synthesis during adjuvant-induced arthritis and with decreased
amplitude of circadian rhythms in immune-cell proliferation and autonomic activity
in lymph nodes and spleen at the clinical phase of the disease. This picture was gen-
erally counteracted by melatonin injection, mainly in old rats
[137]
.
A number of studies were carried out to examine the participation of melatonin
in altered 24-hour rhythms of serum ACTH, GH, prolactin (PRL), LH, and insulin in
rats at the preclinical phase of Freund's adjuvant arthritis
[138]
. The data indicated
that several early changes in levels and 24-hour rhythms of circulating ACTH, PRL,
and LH in FCA-injected rats were sensitive to treatment with melatonin (100 g). An
effect of melatonin treatment on 24-hour variations in hypothalamic 5-HT and DA
turnover during the preclinical phase of Freund's adjuvant arthritis was also appar-
ent
[139]
. FCA injection suppressed circadian rhythmicity of 5-HT turnover in the
anterior hypothalamus, an effect prevented by the previous injection of melatonin.
Melatonin decreased the 5-HT turnover rate in the anterior hypothalamus. Melatonin
also prevented the changes in 5-HT turnover of medial hypothalamus evoked by
Freund's adjuvant. As far as hypothalamic DA turnover, the preventative effect of
melatonin was less clear, as the melatonin sometimes synergized with the myco-
bacterial adjuvant to modify the normal 24-hour pattern detected in hypothalamic
regions
[139]
.
Physiological circulating levels of melatonin at midnight in rats are about
90 pg/ml
[140]
, whereas the melatonin levels achieved within 15 minutes after sys-
temic administration of a 100-g dose are about 30 or 200-ng/ml plasma
[141]
, with
a half-life of about 20 minutes
[140]
. We recently addressed this subject by examin-
ing whether the administration of melatonin to pinealectomized rats, in a way that
reproduced the plasma values and daily rhythm of endogenous melatonin, could
affect immune responses during arthritis development
[142]
. Pinealectomized rats
exhibited a significantly less pronounced inflammatory response, which was restored
