Yakar Ilan, Melamed Rivka, Shakhar Guy, Shakhar Keren, Rosenne Ella, Abudarham Naphtali, Page Gayle G, Ben-Eliyahu Shamgar
Neuroimmunology Research Unit, Department of Psychology, Tel Aviv University, Tel Aviv, Israel.
Ann Surg Oncol. 2003 May;10(4):469-79. doi: 10.1245/aso.2003.08.017.
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.
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.
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.
PGE(2) is a potent in vivo suppressor of NK activity, and its postoperative release may promote tumor recurrence.
前列腺素（PGs）在体外显示可抑制细胞免疫的多种功能。然而，尚不清楚PGs的生理水平是否能在体内抑制细胞免疫，以及这种抑制是否会损害术后宿主对转移的抵抗力。
给Fischer 344大鼠皮下注射剂量为18至300微克/千克的前列腺素E2（PGE2），使血清水平升高约2至4倍。然后，我们评估循环自然杀伤（NK）细胞的数量和活性，以及大鼠对同基因NK敏感肿瘤（MADB106）实验性转移的抵抗力。为了研究手术后内源性释放的PGs是否会损害这些指标，我们测试了剖腹手术是否会对它们产生不利影响，以及环氧化酶合成抑制剂吲哚美辛（4毫克/千克）是否会减弱这些影响。
PGE2剂量依赖性地抑制每个NK细胞的NK活性，并剂量依赖性地增加4小时和24小时的MADB106肺肿瘤滞留（LTR）；240微克/千克的PGE2使3周后计数的肺转移数量增加了四倍。选择性清除NK细胞消除了PGE2对LTR的促进作用。手术显著抑制NK活性并增加MADB106 LTR，吲哚美辛将这些影响减半，而不影响未手术的大鼠。
PGE2是NK活性的一种有效的体内抑制剂，其术后释放可能促进肿瘤复发。
