Prolactin modulates survival and cellular immune functions in septic mice.
BACKGROUND
The immunomodulatory properties of the pituitary hormone prolactin have been demonstrated. It was proposed that prolactin is important in maintaining normal immune response in several pathological states. We investigated the effect of prolactin administration on the survival and cellular immune functions during systemic inflammation.


METHODS
Male NMRI mice were subjected to laparotomy (LAP) or sepsis induced by cecal ligation and puncture (CLP). Mice were treated with either saline (LAP/saline; CLP/saline) or prolactin (LAP/PRL, CLP/RPL; 4 mg/kg s.c.). Survival of septic mice was determined 24 and 48 h after CLP. Forty-eight hours after the septic challenge, the proliferative capacity, cytokine release (IL-2, IL-6, IFN-gamma) and apoptosis of splenocytes were determined. Additionally, monitoring of circulating leukocyte distribution was performed (WBC; CD3+, CD4+, CD8+, B220+, NK1.1+, F4/80+ cells by FASCan).


RESULTS
CLP was accompanied by a mortality of 47% and induced a decrease in splenocyte proliferation and apoptosis rate. Administration of prolactin significantly increased the mortality of septic mice (81%). This was paralleled by a further decrease of splenocyte proliferation and an increased splenocyte apoptosis. In addition, administration of prolactin augmented the sepsis-induced inhibition of IL-2 release, attenuated the sepsis-induced inhibition of IFN-gamma release, and did not affect the release of IL-6. However, prolactin did not affect the sepsis-induced changes of circulating leukocyte subpopulations.


CONCLUSIONS
We conclude that prolactin has profound immunomodulatory properties and that administration of prolactin in pharmacological doses is associated with a decreased survival and an inhibition of cellular immune functions in septic mice.
Oberbeck
Reiner
R
Department of Trauma Surgery, University Hospital of Essen, Essen, Germany. reineroberbeck@hotmail.com
Schmitz
Daniel
D
Wilsenack
Klaus
K
Schüler
Mark
M
Biskup
Claudia
C
Schedlowski
Manfred
M
Nast-Kolb
Dieter
D
Exton
Michael S
MS
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002432:Cecum / Q000601:surgery; D016207:Cytokines / Q000032:analysis; D007111:Immunity, Cellular / Q000187:drug effects*; D007415:Intestinal Obstruction; D007416:Intestinal Perforation; D008026:Ligation; D008297:Male; D051379:Mice; D023421:Models, Animal; D010907:Pituitary Hormones / Q000276:immunology / Q000494:pharmacology*; D011388:Prolactin / Q000276:immunology / Q000494:pharmacology*; D018805:Sepsis / Q000276:immunology*; D016019:Survival Analysis
D016207:Cytokines; D010907:Pituitary Hormones; D011388:Prolactin