Prostaglandin e(2) suppresses NK activity in vivo and promotes postoperative tumor metastasis in rats.
BACKGROUND
Prostaglandins (PGs) were shown in vitro to suppress several functions of cellular immunity. It is unclear, however, whether physiological levels of PGs can suppress cellular immunity in vivo and whether such suppression would compromise postoperative host resistance to metastasis.


METHODS
Fischer 344 rats were administered PGE(2) in doses (18 to 300 micro g/kg subcutaneously) that increased the serum levels approximately 2- to 4-fold. We then assessed the number and activity of circulating natural killer (NK) cells, as well as rats' resistance to experimental metastasis of a syngeneic NK-sensitive tumor (MADB106). To study whether endogenously released PGs after surgery compromise these indices, we tested whether laparotomy adversely affects them and whether a cyclooxygenase-synthesis inhibitor, indomethacin (4 mg/kg), attenuates these effects.


RESULTS
PGE(2) dose-dependently suppressed NK activity per NK cell and dose-dependently increased 4- and 24-hour MADB106 lung tumor retention (LTR); 240 micro g/kg of PGE(2) quadrupled the number of lung metastases counted 3 weeks later. Selective depletion of NK cells abrogated the promotion of LTR by PGE(2). Surgery significantly suppressed NK activity and increased MADB106 LTR, and indomethacin halved these effects without affecting nonoperated rats.


CONCLUSIONS
PGE(2) is a potent in vivo suppressor of NK activity, and its postoperative release may promote tumor recurrence.
Yakar
Ilan
I
Neuroimmunology Research Unit, Department of Psychology, Tel Aviv University, Tel Aviv, Israel.
Melamed
Rivka
R
Shakhar
Guy
G
Shakhar
Keren
K
Rosenne
Ella
E
Abudarham
Naphtali
N
Page
Gayle G
GG
Ben-Eliyahu
Shamgar
S
D000230:Adenocarcinoma; D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D015232:Dinoprostone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005069:Evaluation Studies as Topic; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects*; D008297:Male; D008325:Mammary Neoplasms, Experimental; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344
D016861:Cyclooxygenase Inhibitors; D015232:Dinoprostone; D007213:Indomethacin