title: Suppression of intestinal mucosal natural killer cells by corticosteroids.
abstract: BACKGROUND
  Corticosteroid therapy of patients with inflammatory bowel disease can give rise to systemic side-effects. Budesonide is a topically acting corticosteroid with low systemic bioavailability and is efficacious in the treatment of inflammatory bowel disease. Natural killer cells were previously found to be altered, both systemically and locally, in patients with inflammatory bowel disease. Modulatory effects of budesonide, prednisolone, dexamethasone, and cortisol on peripheral blood NK cells have already been described, but have never been assessed on mucosal NK cells from the intestine.
  
  
  METHODS
  The effect of the synthetic corticosteroids prednisolone and budesonide, the endogenous corticosteroid cortisol, and adrenocorticotropic hormone was analysed on NK cells isolated from the lamina propria of human intestinal resection specimens.
  
  
  RESULTS
  The three corticosteroids suppressed intestinal NK cell activity, not only during the cytotoxicity assay, but also after pre-incubation of the lamina propria mononuclear cells. ACTH, however, did not affect the activity of intestinal NK cells. We previously showed that corticosteroid-suppressed peripheral blood NK cell activity could be restored in vivo, but not in vitro, by the administration of ACTH. In the present study, the in vitro incubation of budesonide- or prednisolone-suppressed mucosal NK cells with cortisol, alone or combined with ACTH, did not revert the suppressed NK cell activity. These findings are similar to our previous observations with peripheral blood NK cells.
  
  
  CONCLUSIONS
  Intestinal mucosal NK cells can be suppressed by systemically as well as locally acting corticosteroids. This suppression in NK cell activity is not reversed by incubation with cortisol and/or ACTH.
authors.affiliation: Department of Gastroenterology and Hepatology, University Hospital Leiden, The Netherlands.
authors.forename: A J
authors.initials: AJ
authors.lastname: Van Ierssel
authors.forename: M A
authors.initials: MA
authors.lastname: Mieremet-Ooms
authors.forename: J M
authors.initials: JM
authors.lastname: Van der Zon
authors.forename: R A
authors.initials: RA
authors.lastname: Van Hogezand
authors.forename: G
authors.initials: G
authors.lastname: Griffioen
authors.forename: C B
authors.initials: CB
authors.lastname: Lamers
authors.forename: H W
authors.initials: HW
authors.lastname: Verspaget
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D019819:Budesonide; D018938:Caco-2 Cells; D003602:Cytotoxicity, Immunologic; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000276:immunology; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000494:pharmacology; D011282:Pregnenediones / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D011282:Pregnenediones; D019819:Budesonide; D000324:Adrenocorticotropic Hormone; D011239:Prednisolone; D006854:Hydrocortisone