Effect of differential housing in mice on natural killer cell activity, tumor growth, and plasma corticosterone

Various forms of stress have been shown to alter natural killer (NK) cell activity and tumorigenesis; however, few studies have measured these two variables simultaneously. Isolation of mice was utilized as a model of stress by which to study NK cell activity and pulmonary metastatic response following a tumor challenge. Male C3H mice were group or individually housed for 3 weeks, after which CIRAS 3 fibrosarcoma tumor cells or the tumor vehicle was injected intravenously (tail vein), NK cell activity, pulmonary metastasis, and plasma corticosterone were measured 1, 7, and 21 days following tumor cell inoculation. Individually housed mice, irrespective of tumor or vehicle condition, had a higher NK response on Day 1 relative to group-housed animals (P less than 0.001). By Day 21, tumor condition, rather than housing, was the major significant factor affecting NK activity (P less than 0.001). Nevertheless, individually housed, tumor-injected mice still had higher NK activity compared with the other treatment groups on Day 21. No effect of housing condition was present for the incidence of pulmonary metastases or frequency of metastases in affected animals. Plasma corticosterone levels generally increased over the study period, with no housing or injection effects at Days 1 and 7. Individually housed, vehicle-injected mice had higher corticosterone levels at Day 21 (P less than 0.01). These data suggest that in response to housing condition, NK cell activity differs in tumor-bearing mice and vehicle controls. Furthermore, CIRAS 3 pulmonary tumor formation is not affected by differences in NK activity consequent to housing condition. Plasma corticosterone does not appear to be a major in vivo regulator of NK activity in this experimental tumor system. Finally, the interpretation of housing effects on NK activity and plasma corticosterone levels depends on the temporal window in which sampling occurs.