Induction of natural killer cell activity and perforin and granzyme B gene expression following continuous culture or short pulse with interleukin-12 in young and old mice

Katy Argentati, Beatrice Bartozzi, Giovanni Bernardini, Grazia Di Stasio, Mauro Provinciali

Research output: Contribution to journalArticle

Abstract

Anticancer immunotherapy with cytokines is often limited by the occurrence of severe toxicity, particularly in older age groups, which are characterized by a reduced tolerance to antineoplastic therapies. We, and others, have recently demonstrated the efficacy of pulsing procedures with IL-2 as a new therapeutic strategy to induce antitumor cytotoxic cells. The aim of this paper was to evaluate the effect of IL-12 on NK cell activity in young and old mice and to investigate the possibility of inducing NK cytotoxicity and perforin and granzyme B gene expression through a brief exposure of spleen lymphocytes from young and old mice to IL-12. Pulsed lymphocytes were compared with non-pulsed cells cultured continuously in IL-12. IL-12 was able to boost both endogenous and IL-2-induced NK cell activity in young and old mice; the levels of cytotoxicity were lower in old than in young animals although the relative increase of IL-12 plus IL-2 versus IL-2 alone was greater for old mice. Comparable levels of NK cell activity were obtained in pulsed (5 min-1 hour) and non-pulsed lymphocytes from both young and old mice after one or three days of culture. The efficacy of the pulsing procedure was evident in both endogenous and IL-2-induced NK cytotoxicity. The mRNA encoding perforin and granzyme B were markedly and similarly enhanced in both IL-12-pulsed and non-pulsed lymphocytes in comparison with control cells. The results demonstrate the effectiveness of IL-12 pulsing in inducing antitumor cytotoxic cells, suggesting the possibility of using IL-12 pulsing, alone or in combination with IL-2, in the immunotherapy of both young and old subjects.

Original languageEnglish
Pages (from-to)59-65
Number of pages7
JournalEuropean Cytokine Network
Volume11
Issue number1
Publication statusPublished - 2000

Keywords

  • Aging
  • Granzyme
  • IL-12 pulse
  • Mice
  • NK cell activity
  • Perforin

ASJC Scopus subject areas

  • Cell Biology
  • Immunology

Fingerprint Dive into the research topics of 'Induction of natural killer cell activity and perforin and granzyme B gene expression following continuous culture or short pulse with interleukin-12 in young and old mice'. Together they form a unique fingerprint.

  • Cite this