title: The corticosteroid-induced inhibitory effect on NK cell function reflects down-regulation and/or dysfunction of triggering receptors involved in natural cytotoxicity.
abstract: Corticosteroids are known to inhibit NK cell functions. However no information is available on whether such inhibition may affect the expression and/or the function of receptors involved in NK cell activation. In an attempt to analyze this point, we studied peripheral blood NK cells isolated from pediatric patients undergoing allogeneic BM transplantation. NK cells were analyzed before, during and after methylprednisolone administration to treat acute graft-versus-host disease. In NK cells freshly isolated from peripheral blood during methylprednisolone treatment, the surface expression of activating receptors, particularly NKp46 and NKp30, was consistently reduced. Such impaired expression could also be detected after 5 days of culture in IL-2. Such cultured NK cells also failed to express the IL-2-inducible NKp44 receptor. Accordingly, cytotoxicity against different tumor target cell lines was sharply reduced. The effect on NK cells isolated from healthy individuals and cultured in the presence of methylprednisolone was also analyzed. A similar inhibitory effect occurred in the expression of activating NK receptors. In addition, a sharp impairment of NK cytotoxicity against different tumor target cell lines or immature DC was detected.
authors.affiliation: Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Vitale
authors.forename: Laura
authors.initials: L
authors.lastname: Chiossone
authors.forename: Claudia
authors.initials: C
authors.lastname: Cantoni
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Morreale
authors.forename: Francesca
authors.initials: F
authors.lastname: Cottalasso
authors.forename: Sara
authors.initials: S
authors.lastname: Moretti
authors.forename: Angela
authors.initials: A
authors.lastname: Pistorio
authors.forename: Riccardo
authors.initials: R
authors.lastname: Haupt
authors.forename: Edoardo
authors.initials: E
authors.lastname: Lanino
authors.forename: Giorgio
authors.initials: G
authors.lastname: Dini
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Moretta
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Mingari
mesh_terms: D000293:Adolescent; D016026:Bone Marrow Transplantation / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D003601:Cytotoxicity Tests, Immunologic; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D005434:Flow Cytometry; D005938:Glucocorticoids / Q000276:immunology* / Q000494:pharmacology; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008775:Methylprednisolone / Q000276:immunology* / Q000494:pharmacology; D012313:RNA / Q000737:chemistry / Q000235:genetics; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D005938:Glucocorticoids; D011971:Receptors, Immunologic; D012313:RNA; D008775:Methylprednisolone