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Abstract: Perioperative suppression of NK activity has been suggested to compromise host resistance to tumor progression. Here, we sought to develop a clinically applicable preoperative regimen to prevent immunosuppression and promotion of metastasis by stress or surgery. The synthetic ds-RNA, poly I–C, was used in vivo in F344 rats, based on its alleged in vitro ability to protect immunocytes from suppression by cAMP elevating agents. Different regimens of poly I–C were studied in controls and in rats subjected to a pharmacological stressor, swim stress, or surgical stress. Resistance to lung experimental metastasis of the syngeneic non-immunogenic MADB106 mammary adenocarcinoma was assessed. Numbers of circulating and marginating-pulmonary NK cells and their cytotoxicity against the MADB106 and YAC-1 target lines were also studied. Our findings established a regimen of repeated low-dose poly I–C administration with minimal side effects (0.2mg/kg i.p. 5, 3, and 1day before tumor inoculation). This regimen, while hardly affecting resistance levels in non-stressed animals, prevented all stressors from promoting metastases. These beneficial effects occurred in the presence of a primary tumor and in both sexes. Poly I–C increased the numbers of NK cells, and, on a per NK cell basis, while not increasing cytotoxicity, profoundly protected marginating-pulmonary NK cells from suppression by surgery. This study suggests a non-toxic clinically translatable prophylactic use of poly I–C to target the critical perioperative period. By increasing the number of marginating-pulmonary NK cells, and by transforming them into a mode of resistance to immunosuppression, this approach may reduce postoperative metastasis in cancer patients. [Copyright &y& Elsevier]

Arad M, Atzil S, Shakhar K, Adoni A, Ben-Eliyahu S. Poly I-C induces early embryo loss in F344 rats: a potential role for NK cells. AJRI 2005; 54:49–53 © Blackwell Munksgaard, 2005 Natural killer (NK) cells were associated with first trimester embryo loss. The current study in the inbred F344 rat assessed the role of NK cells in mediating resorptions caused by poly I-C, a non-specific immunostimulator. On fifth day of gestation, rats were injected intraperitoneally with anti-NKR-P1 (1.5 mg/kg, i.p.) to deplete NK cells, and with mouse serum or saline to control for non-specific effects. Poly I-C (4 mg/kg, i.p.) or vehicle were administered 2 days later. Resorptions were assessed on day 13.5. Poly I-C significantly elevated resorption rates, and anti-NKR-P1 abolished this effect. Body weight was reduced in all rats treated with poly I-C, including NK-depleted rats. This indicates the ability of NK-depleted rats to respond to poly I-C, yet to refrain from the resorption-promoting effects of poly I-C. This study suggests a role for NK cells in mediating poly I-C-induced resorptions. [ABSTRACT FROM AUTHOR]