The pineal hormone melatonin, due to its lipophilic nature, has access to e
very cell and every part of a cell in the body, suggesting that it could ex
ert effects on blood immune cells. The regulation of the activation of mono
cytes may be important in a number of diseases, especially pathophysiologic
al conditions associated with inflammatory reactions. Considering this, a s
tudy on the effect of melatonin on monocytes in whole blood was carried out
. Melatonin added at a final concentration of 5 ng/mL to whole blood in vit
ro reduced lipopolysaccharide (LPS)-induced tissue factor (TF) activity in
monocytes by 55% in blood from a group of subjects with melatonin-sensitive
cells. At even lower concentrations of melatonin (20-50 pg/mL) and in the
physiological range, a trend of suppressed LPS-induced TF activity by appro
ximate to 20% was seen. A further indication of a downregulation of LPS-sti
mulated monocytes by melatonin was shown by its reduction of LPS-induced tu
mor necrosis factor (TNF). Twenty to one hundred pg/mL melatonin caused a s
ignificant reduction of LPS-induced TNF production by approximate to 25-30%
. In contrast, melatonin at a final concentration of 10 pg/mL, added to who
le blood incubated with LPS and also the phorbol ester, PMA, caused a signi
ficant rise of 25%; whereas 100 pg/mL enhanced LPS + PMA-induced TNF by app
roximate to 80% as compared to LPS + PMA alone. These effects were not dete
ctable during the winter darkness of Tromso (70 degrees N), probably due to
the high content of melatonin in the blood even at daytime. These results
show that melatonin may have a beneficial effect by suppressing the express
ion of TF activity in LPS-stimulated monocytes. Furthermore, the results in
dicate that LPS-induced TF in monocytes of whole blood is independent of pr
otein kinase C (PKC) activation. Melatonin is probably amplifying cellular
activation reactions that are PKC-dependent. This may be physiologically im
portant in upregulation of the immune system.