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Blood, 1 July 2005, Vol. 106, No. 1, pp. 158-166.
Prepublished online as a Blood First Edition Paper on March 8, 2005; DOI 10.1182/blood-2004-08-3232.
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Submitted August 20, 2004
Accepted February 22, 2005
A potential role for hydrocortisone in the positive regulation of IL-15-activated NK cell proliferation and survival
Sonia A Perez*, Louisa G Mahaira, Fillio J Demirtzoglou, Panagiota A Sotiropoulou, Panayotis Ioannidis, Eleni G Iliopoulou, Angelos D Gritzapis, Nectaria N Sotiriadou, Constantin N Baxevanis, and Michael Papamichail
Cancer Immunology and Immunotherapy Center, Saint Savas Hospital, Athens, Greece
* Corresponding author; email: perez{at}ciic.gr.
Although glucocorticoids (GC) have been mainly described to act as anti-inflammatory and immunosuppressive drugs, they may also positively influence the immune system. In the present study, we demonstrate for the first time that hydrocortisone (HC), in synergy with interleukin-15 (IL-15), induces a dramatic increase in the expansion of peripheral blood-derived CD56+ cells, favoring the preferential outgrowth of classical natural killer (CD56+CD3- NK) over CD56+CD3+ NKT cells. HC plus IL-15-driven CD56+ cells exhibited an increased potential for cytokine production with no impairment in their NK and lymphokine-activated killer (LAK) activities. Elevated levels of GC induced leucine zipper protein (GILZ) mRNA were detected in both NK and NKT cells cultured with HC and IL-15, in comparison to IL-15 alone. Phosphorylation status of signal transducer and activator of transcription 5 (STAT5) was not affected by the presence of HC in either of the populations. On the contrary, HC differentially affected the IL-2/IL-15R  - and  -chain surface expression and the phosphorylation levels of extracellular signal-regulated kinases 1/2 (ERK1/2) in IL-15 activated NK and NKT cells. Our data ascribe a novel role to GC on mature NK cell expansion and function and open new perspectives for their use in cellular adoptive cancer immunotherapy.
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