Effect of host age upon interleukin-2-mediated anti-tumor responses in a murine fibrosarcoma model

The age-associated decline in immune function may be an important factor in both the pathogenesis of neoplastic diseases and the response to immunopharmacological therapies. With the increased efforts to develop immunotherapy with such agents as interferon and interleukin-2 (IL-2), the question of the effect of host age upon response is of practical importance. Phase I and phase II clinical trials of IL-2 have included primarily young patients, and toxicity and efficacy have not been reported with specific reference to host age. In this study, we examined young and old mice with regard to in vitro natural killer and lymphokine-activated killer (LAK) cell functions. We also assessed the effects of exogenously administered recombinant human IL-2 in tumor-bearing mice of various ages. We found that natural killer cell function was demonstrably lower in old mice but that LAK cell function was comparable (young versus old). Furthermore, IL-2 treatment was successful in increasing survival time in old mice, similar to results in young mice. Our observations allow the prediction that immune senescence per se does not preclude successful anti-neoplastic treatment with IL-2.