Age-associated Decline In Immune Function Research Articles

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.

Age-associated decline in cardiac allograft rejection

The influence of age on cardiac allograft rejection was studied in 57 consecutive recipients. Twenty-one subjects were 54 years of age or older (mean, 57.7 ± 0.6 years [± SEM]; range, 54 to 63 years) and 36 subjects were 52 years of age or younger (mean, 39.9 ± 1.8 years; range, 16 to 52 years; p <0.001). The older recipients had fewer rejection episodes during the first four months following cardiac transplantation (0.24 ± 0.05 episodes per month versus 0.72 ± 0.09 episodes per month; p <0.001) and during the total duration of follow-up (0.20 ± 0.03 episodes per month versus 0.40 ± 0.07 episodes per month; p = 0.045), and experienced their first rejection episode later (50.4 ± 4.0 days versus 27.7 ± 8.5 days; p = 0.008). Younger age was found to add significantly as a predictor of rejection in a multivariate analysis that controlled for sex, immunosuppressive agents, cause of heart failure, and pretransplantation lymphocyte cross-match status (r = 0.64, p <0.05). Decreased rejection frequency occurred without a concomitant increase in the serious infection rate (67 percent in both groups). The 12-month actuarial survival was 100 percent in the older group and 94 percent in the younger group (p = NS). Decreased rejection in the older recipients is likely a manifestation of an age-associated decline in immune function and might represent an advantage in transplantation for carefully selected older patients.