Dehydroepiandrosterone sulfate enhances natural killer cell cytotoxicity in humans via locally generated immunoreactive insulin-like growth factor I

S. B. Solerte, M. Fioravanti, G. Vignati, A. Giustina, L. Cravello, E. Ferrari

Research output: Contribution to journalArticle

Abstract

Experimental and clinical investigations suggest the hypothesis that dehydroepiandrosterone sulfate (DHEAS) can positively influence natural killer (NK) immunity via locally produced insulin-like growth factor I (IGF-I) from NK cells. In the present study, the NK cell cytotoxicity (NKCC) and IGF-I levels in the supernatant of NK cells were studied at baseline and after exposure to various molar concentrations of DHEAS (from 10-5-10-8 mol/L·mL/7.75 x 106 NK cells) in healthy subjects of young and old age. DHEAS-induced NKCC was also determined after DHEAS coincubation with somatostatin-14 (10-6 mol/L·mL/7.75 x 106 NK cells) and with interleukin-2 (IL-2; 100 IU/mL·7.75 x 106 NK cells). NK cells were previously isolated by Ficoll-Hypaque density gradient and then by immunomagnetic procedure; the purity obtained was 97 ± 1%. NKCC was determined against K562 tumoral targets. We observed that the increase in NKCC after DHEAS exposure was dose dependent and was correlated with the amount of IGF-I released in the supernatant of cultured NK cells. NKCC and IGF-I generation from NK cells were more elevated in healthy elder subjects than in healthy young subjects. The coincubation of DHEAS with somatostatin-14 significantly suppressed NKCC and IGF-I release from NK in both groups, whereas higher NKCC was found after DHEAS plus IL-2 exposure than after incubation with DHEAS alone. Taken together, this study suggests a role for NK-generated IGF-I in the modulation of NKCC by DHEAS in humans. Although DHEAS may contribute to the IL-2-mediated NKCC, its activity on NK cytolytic function can be dependent on a autocrine mechanism (IGF-I-mediated), probably independent of cytokine activation. The higher NKCC response to DHEAS found in old subjects than in younger might counterbalance the age-dependent decline in circulating, DHEAS, thus contributing to maintain the pattern of NK immunity during aging.

Original languageEnglish
Pages (from-to)3260-3267
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Volume84
Issue number9
Publication statusPublished - 1999

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ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

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