Age Related Natural Killer Activity of Peripheral Blood Lymphocytes from Healthy Subjects and Cancer Patients. A Comparative in Vitro Study with Interleukin-2

Abstract

Aims and Beckground Natural killer (NK) cell activity is known to be depressed in neoplastic diseases, and ageing influences the cytotoxicity of NK cells. However, very little information is available on the responsiveness of NK cells of cancer patients to the stimulating effects of interleukin-2 (IL-2) as a function of age. Methods We assessed in vitro IL-2 induced modulation of NK activity in peripheral blood lymphocytes (PBL) from 7 young (30-50 years) and 9 elderly (55-78 years) male patients with carcinoma of the oral cavity. In these patients generation of lyphokine activated killer (LAK) activity was also studied. NK and LAK activity of PBL were measured in 14 age and sex matched healthy volunteers as who served as conrols. Cytotoxicity of the NK and LAK cells was assayed against NK sensitive K562 and NK resistant Daudi cells in 4-h 51 Cr-release assays. Results NK activity in the cancer patients was significantly lower than that in healthy volunteers. In both groups the younger subjects had higher NK activity than the elderly ones. NK cells of both young and elderly healthy controls responded similarly to 24-hour in vitro exposure to human recombinant IL-2 (rIL-2, 100 u/ml) with highly increased cytotoxicity. Though there was significant enhancement of NK activity with rIL-2 in both young and elderly cancer patients, the rIL-2 induced NK cytotoxicity in the elderly patients was much lower than the basal level of NK activity of the age matched controls. Interestingly, LAK activity, generated by 3-7 days of in vitro exposure of PBL to rlL-2 was comparable in the cancer patients and healthy volunteers Conclusion The data suggest serious impairment of NK function in elderly patients with oral carcinoma. Generation of LAK activity with exogenous IL-2 could be an important modality of treatment in these patients.