The present study examined the response of macrophages/microglia to multipl
e injections of melatonin in the pineal gland and different regions of the
brain. The macrophages;microglia showed a significant increase in cell numb
ers and upregulation of complement type 3 receptors (CR3), major histocompa
tibility complex class I (MHC I) and class II (MHC II) antigens, and antige
ns of monocyte/macrophage lineage, as detected by the antibodies OX-42, OX-
18, OX-6, and EDI, respectively. The upregulation of the above antigens was
observed in 1-d-old rats given daily injections of melatonin and killed at
7-11 d of age; no noticeable change was observed at earlier time intervals
. The macrophages/microglia expressing the above antigens appeared round an
d showed a vacuolated cytoplasm compared with ramified cells in the control
rats. Upregulation of CD4 antigens as detected with the antibody W3/25 was
also observed in macrophages/microglia in the corpus callosum and epiplexu
s cells in the lateral ventricles, but not in the pineal gland and the cere
bral cortex in the same age group. In rats killed between 2 and 5 d, and at
14 d of age after melatonin treatment, the immunoreactivities of macrophag
es/microglia with the above mentioned antibodies were comparable to cells i
n the control rats. Immunoreactive cells were not detected in ally of the a
ge groups in melatonin-treated or control rats with the antibodies W3/13 an
d OX-33, which are markers for T and B lymphocytes. It is concluded that CR
3 receptors, MHC antigens, and CD4 antigens on macrophages/microglia are up
regulated following melatonin administration. On the other hand, once the m
elatonin treatment is discontinued the expression of the various antigens/r
eceptors returns to normal levels, suggesting that increased immune potenti
ality and its maintenance in these cells require the continuous action of t
he drug.