Effects of restraint stress on inoculated tumor growth and immune response in rats

Rats were given injections s.c. of mammary adenocarcinoma cells which developed into undifferentiated carcinomas within a few days. The animals were either left alone or were stressed by restraint for 3 h a day for 11 days and then left for 12 days undisturbed to recover. During this schedule, some animals were sacrificed immediately after the 11-day stress period, whereas others were allowed the 12-day recovery period; unstressed animals were sacrificed as controls on these 2 days. Tumor burden was significantly increased during stress and markedly decreased after the recovery period as compared to unstressed rats. Higher mitotic activity was seen in the tumors of rats which recovered from stress. The immune system responded differently to stress in healthy and tumor-bearing animals. In the tumor-bearing animals, leukocytes were decreased by stress and increased after the recovery period. Lymphocytes were increased, and neutrophiles and large granular lymphocytes were decreased after the recovery period. Total T-cells and suppressor T-cells were decreased during stress and increased during recovery. The percentage of T-cell populations was unaffected by stress, but the percentage of suppressor T-cells increased during recovery. Natural killer cell activity was unaffected by stress but increased after the recovery period. These results indicate that (a) stress and recovery from stress differentially affect tumor development and growth, (b) stress and recovery from stress cause different effects on the immune system in healthy or tumor-bearing animals, (c) stress and recovery from stress stimulate or inhibit different parts of the immune system, and (d) a decreased lymphocyte count and total and suppressor T-cell numbers correlated best with enhanced tumor growth, whereas increased numbers of neutrophils, large granular lymphocytes, total and suppressor T-cells, natural killer cell activity, and a decreased percentage of T-suppressor cells correlated best with depressed tumor growth.