Suppression of intestinal mucosal natural killer cells by corticosteroids.
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.
Van Ierssel
A J
AJ
Department of Gastroenterology and Hepatology, University Hospital Leiden, The Netherlands.
Mieremet-Ooms
M A
MA
Van der Zon
J M
JM
Van Hogezand
R A
RA
Griffioen
G
G
Lamers
C B
CB
Verspaget
H W
HW
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
D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D011282:Pregnenediones; D019819:Budesonide; D000324:Adrenocorticotropic Hormone; D011239:Prednisolone; D006854:Hydrocortisone