The immunoregulatory effects of prolactin in mice are time of day dependent.
The effects of timed administration of PRL on immune activities were investigated in male BALB/c mice. Ten daily injections of PRL (1 mg/kg) were made 0/24, 4, 8, 12, 16, or 20 h after light onset (HALO). On day 11, spleen cells were harvested between 1-3 HALO and cocultured with gamma-irradiated C57BL/6 spleen cells for 5 days, and proliferative responses to alloantigen were assayed (mixed lymphocyte reaction). When given in vivo at 4-12 HALO, PRL strongly stimulated proliferation by more than 2-fold, whereas PRL injections when given at 24 HALO substantially inhibited proliferation and had no effect when given at 16-20 HALO. When endogenous PRL secretion was stimulated for 7 days with injections of domperidone or 5-hydroxytryptophan, the splenocyte response increased by 48% and 64%, respectively, when injections were given at 9-10 HALO, but did not increase when they were given at 23-0 HALO. Inhibition of endogenous PRL secretion for 7 days with bromocriptine (2.5 mg/kg.day) inhibited splenocyte responsiveness by 40% when injected at 9 HALO, but had no effect when administered at 0 HALO. Furthermore, such bromocriptine treatment inhibited T- and B-cell mitogenic responses to Concanavalin-A (by 48%) and lipopolysaccharide (38%) when administered at 10, but not 0, HALO. In a manner similar to mixed lymphocyte reaction responses, daily PRL injections for 10 days at 11 HALO stimulated (40%) the in vivo delayed-type hypersensitivity response to antigen (azobenzenearsonate), whereas injections at 0 HALO were nonstimulatory. Bromocriptine treatment (1.5 mg/kg.day) suppressed the delayed-type hypersensitivity response (43% less than the control value) when administered at 10-12 HALO, but had no effect when administered at light onset. Timed PRL injections for 28 days in adult mice increased (42%) the total thymic cell number when administered at 11 HALO, but had no effect when injected at 0 HALO. Together, these results show that immunocyte responsiveness to PRL is time of day dependent. Thus, these findings support an essential and heretofore unrecognized circadian role in PRL regulation of immunity.
Cincotta
A H
AH
Wellman Laboratories of Photomedicine, Massachusetts General Hospital, Boston 02114, USA.
Knisely
T L
TL
Landry
R J
RJ
Miers
W R
WR
Gutierrez
P J
PJ
Esperanza
P
P
Meier
A H
AH
D000818:Animals; D001971:Bromocriptine / Q000494:pharmacology; D002478:Cells, Cultured; D002940:Circadian Rhythm; D005720:Gamma Rays; D006968:Hypersensitivity, Delayed; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D007959:Lymphocyte Culture Test, Mixed; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000528:radiation effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011388:Prolactin / Q000494:pharmacology*; D013154:Spleen / Q000187:drug effects / Q000276:immunology* / Q000528:radiation effects
D008070:Lipopolysaccharides; D001971:Bromocriptine; D011388:Prolactin