Time-dependent effects of stressor application on metastasis of tumor cells in the lung and its regulation by an immunomodulator in mice

The effects of the timing of stressor application on transplanted tumor cel ls and its possible regulation by an immunomodulator was investigated. Male C57 BL/6N mice were subjected to rotational stressor for 7 days relative t o tumor cell inoculation: stressor after inoculation of Lewis lung cancer c ells, stressor during inoculation and stressor before inoculation. Stressor application and tumor cell inoculation induced transient decreases in body weight, particularly in mice stressed after inoculation. The mice exposed to the stressor during inoculation or before inoculation showed significant increases in the number of metastatic foci relative to control mice. Early administration of an immunomodulator, PSK, significantly attenuated the in crease of metastatic foci in stressed mice. The weights of thymus gland and spleen at 14 days after inoculation were similar in the three stressor gro ups and the control group. Application of the stressor reduced NK cell acti vity of the normal mice as well as tumor bearing mice. The lowest pre-inocu lation NK cell activity was observed in mice stressed for 7 days beginning on the day of inoculation. The NK cell activity decreased in the tumor bear ing mice which were stressed at the time of tumor inoculation. Decreased NK cell activity was reversed at day 14 after tumor inoculation. The mice exp osed to the stressor after inoculation showed lowest level of NK cell activ ity relative to mice exposed to the stressor before or during inoculation. The treatment of mice with PSK reduced these changes significantly. The pre sent results suggest that the rotational stress reduces splenic NK cell act ivity, which may influence the magnitude of tumor metastasis, depending on the time of tumor cell injection. Further, administration of an immunomodul ator may counteract the reduction of the NK cell activity. (C) 1999 Elsevie r Science Ltd. All rights reserved.