A potential role for hydrocortisone in the positive regulation of IL-15–activated NK-cell proliferation and survival

• Published in: Blood 2005-07, Vol.106 (1), p.158-166
• Main Authors: Perez, Sonia A., Mahaira, Louisa G., Demirtzoglou, Fillio J., Sotiropoulou, Panagiota A., Ioannidis, Panayotis, Iliopoulou, Eleni G., Gritzapis, Angelos D., Sotiriadou, Nectaria N., Baxevanis, Constantin N., Papamichail, Michael
• Format: Article
• Language: English
• Subjects: Adoptive Transfer - methods; Anti-Inflammatory Agents - pharmacology; Antineoplastic agents; Biological and medical sciences; Burkitt Lymphoma; CD3 Complex - metabolism; CD56 Antigen - metabolism; Cell Division - drug effects; Cell Survival - drug effects; Cells, Cultured; DNA-Binding Proteins - metabolism; Humans; Hydrocortisone - pharmacology; Immunopathology; Immunotherapy; Immunotherapy (general aspects); Interleukin-15 - metabolism; Interleukin-2 - metabolism; K562 Cells; Killer Cells, Natural - cytology; Killer Cells, Natural - drug effects; Killer Cells, Natural - metabolism; Medical sciences; Milk Proteins - metabolism; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - metabolism; Pharmacology. Drug treatments; Phosphorylation; Receptors, Interleukin-15; Receptors, Interleukin-2 - genetics; RNA, Messenger - analysis; STAT5 Transcription Factor; Trans-Activators - metabolism; Transcription Factors - genetics
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2004-08-3232

Although glucocorticoids (GCs) have been described as acting mainly 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+ natural killer T (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) messenger RNA (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 β- and γ-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 GCs on mature NK-cell expansion and function and open new perspectives for their use in cellular adoptive cancer immunotherapy.