Corticostatins/defensins inhibit in vitro NK activity and cytokine production by human peripheral blood mononuclear cells

• Published in: Regulatory peptides 1996-04, Vol.62 (1), p.13-21
• Main Authors: Masera, Rosa Gabriella, Bateman, Andrew, Muscettola, Michela, Solomon, Samuel, Angeli, Alberto
• Format: Article
• Language: English
• Subjects: Adrenal Glands - metabolism; alpha-Defensins; Analysis of Variance; Animals; Anti-Infective Agents - immunology; Anti-Infective Agents - metabolism; Anti-Infective Agents - pharmacology; Antibody Formation; Biological and medical sciences; Blood Proteins - immunology; Blood Proteins - metabolism; Blood Proteins - pharmacology; Chromatography, High Pressure Liquid; Concanavalin A - pharmacology; Cytokines - biosynthesis; Defensins; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Hormone Antagonists - immunology; Hormone Antagonists - metabolism; Hormone Antagonists - pharmacology; HP-1; HP-4; Humans; Hydrocortisone - pharmacology; Hypothalamic-pituitary-adrenal axis; Hypothalamus - metabolism; Immunobiology; Interferon-gamma - biosynthesis; Interferon-gamma - pharmacology; Interleukin-2 - pharmacology; Interleukin-6 - biosynthesis; Killer Cells, Natural - cytology; Killer Cells, Natural - drug effects; Killer Cells, Natural - immunology; Lymphocyte; Mitogen; Modulation of the immune response (stimulation, suppression); Neutrophils - cytology; Neutrophils - drug effects; Neutrophils - immunology; Peptides - immunology; Peptides - metabolism; Peptides - pharmacology; Phytohemagglutinins - pharmacology; Pituitary Gland - metabolism; Rabbits; Radioimmunoassay; Recombinant Proteins - pharmacology; T-Lymphocytes - cytology; T-Lymphocytes - drug effects; T-Lymphocytes - immunology
• ISSN: 0167-0115; 1873-1686
• DOI: 10.1016/0167-0115(95)00150-6

Corticostatins/defensins are a family of cationic peptides recently isolated from phagocytotic cells of the myeloid lineage. Natural killer (NK) cells are spontaneously cytotoxic large granular lymphocytes that are involved in immunosurveillance against cancer and infections. Their activity is modulated by hormones of the hypothalamic-pituitary-adrenal axis. We wished to determine whether two human corticostatins/defensins, HP-1 and HP-4, are able to change in vitro the spontaneous NK activity of human peripheral blood mononuclear cells (PBMC) and the responses either to the stimulatory cytokines immune interferon (IFN-γ) or interleukin 2 (IL-2) and to the inhibitory hormone cortisol. NK cell activity was measured in a 4-h direct cytotoxicity assay with K562 cells as a target. HP-1 and HP-4 (10 −8−10 −9 M) significantly inhibited the spontaneous and cytokine-inducible NK activity, and increased the cortisol-dependent inhibition. Radioimmunoassay of HPLC purified fractions obtained from sonicated NK cells showed HP-1 in the two cell preparations examined. We also evaluated the effects of HP-1 and HP-4 (10 −8 M − 10 −9 M) upon IFN-γ and interleukin 6 (IL-6) production by PBMC stimulated with phytohemagglutinin (PHA) or concanavalin A (ConA). IFN-γ was titrated with the biological assay using WISH cells as indicators and vescicular stomatitis virus (VSV) as the challenge virus. IL-6 was measured using an enzyme amplified sensitivity immunoassay. Both HP-1 and HP-4 significantly reduced cytokine production. Our data indicate that corticostatins/defensins are novel modulators of lymphocyte functions in vitro. Their immunodepressing properties could add complexity and plasticity to hypothalamic-pituitary-adrenal-cytokine circuits in vivo.