[In vitro effects of peptides of the corticostatin/defensin family on production of mitogen-induced cytokines].
Cytokines are autocrine, paracrine and endocrine glycoproteins that interact with specific cell receptors and have pleiotropic effects. Increasing evidence indicates that cytokines, immune interferon (IFN-gamma) and interleukin 6 (IL-6) among others, modulate hypothalamic-pituitary-adrenal function. Corticostatins/defensins are a family of cationic peptides recently isolated from phagocytic cells of myeloid lineage. Four peptides have been isolated from human neutrophils: HP-1, 2, 3 and 4. As defensins they participate in immunosurveillance against viruses, bacteria and fungi. Some members of the family are also able to inhibit ACTH-induced steroidogenesis. Among human peptides, only HP-4 is corticostatic. We previously demonstrated that HP-1 and HP-4 inhibit in vitro the spontaneous and cytokine-inducible natural killer activity of human peripheral blood mononuclear cells (PBMC) and potentiate cortisol-dependent inhibition. The present work was carried out to determine whether two human corticostatins/defensins, HP-1 and HP-4, were able to modulate in vitro IFN-gamma and IL-6 production by human PBMC stimulated with phytohemagglutinin or Concanavalin A. IFN-gamma was titrated using biological assay with WISH cells as indicators and vesicular stomatitis virus as the challenge virus. IL-6 was measured by means of enzyme amplified sensitivity immunoassay. Both HP-1 and HP-4 significantly reduced cytokine production. Our data indicate that HP-1 and HP-4 are novel modulators of lymphocyte functions in vitro. Their depressing properties on ACTH-induced steroidogenesis and on cytokine production add complexity to neuroendocrine-immune circuits involving hypothalamic-pituitary-adrenal function.
Masera
R G
RG
Dipartimento di Scienze Cliniche e Biologiche, Università degli Studi di Torino.
Muscettola
M
M
Tanganelli
C
C
Grasso
G
G
Bateman
A
A
Solomon
S
S
Angeli
A
A
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D001770:Blood Bactericidal Activity; D001798:Blood Proteins / Q000494:pharmacology*; D003208:Concanavalin A / Q000494:pharmacology; D003366:Cosyntropin / Q000037:antagonists & inhibitors*; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis*; D023082:Defensins; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins; D007371:Interferon-gamma / Q000032:analysis / Q000096:biosynthesis; D015850:Interleukin-6 / Q000032:analysis / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008934:Mitogens / Q000494:pharmacology; D009504:Neutrophils / Q000276:immunology*; D010455:Peptides / Q000494:pharmacology*; D010835:Phytohemagglutinins / Q000494:pharmacology; D023084:alpha-Defensins
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D000935:Antifungal Agents; D001798:Blood Proteins; D016207:Cytokines; D023082:Defensins; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6; D008934:Mitogens; D010455:Peptides; D010835:Phytohemagglutinins; D023084:alpha-Defensins; C406413:human neutrophil peptide 1; C406428:human neutrophil peptide 4; D003208:Concanavalin A; C054598:corticostatin; D003366:Cosyntropin; D007371:Interferon-gamma