DECREASES IN MACROPHAGE-MEDIATED ANTITUMOR-ACTIVITY WITH AGING

We have demonstrated that immunotherapy of young (6-10 weeks old), and aged, (greater than 24 months old), tumor bearing mice with biologica l response modifiers enhanced survival and inhibited tumor growth, whi le treatment of aged mice had little or no effect. We hypothesized tha t the antitumor activity in young mice was principally mediated by act ivated macrophages (M phi) and predicted that the change in aged mice was caused by an intrinsic M phi defect which develops with advancing age. To directly test our hypothesis, we examined the antitumor activi ty of resident peritoneal M phi, purified and activated in vitro with IFN gamma plus LPS. Paralleling the results seen in vivo, M phi from a ged mice exhibited reduced antitumor activity in comparison with M phi from younger mice. Moreover, there was reduced capacity of in vitro a ctivated M phi from aged mice to produce TNF, IL-1 and nitric oxide, w hich are critical monokines and effector molecules that have been esta blished to either directly inhibit tumor growth or cause tumor cell de struction. These studies establish that peritoneal M phi from aged mic e have an intrinsic defect which prevents them from fully expressing t heir antitumor potential.