Dexamethasone suppresses interleukin-22 associated with bacterial infection in vitro and in vivo.
Interleukin (IL)-22 production triggered by innate immune mechanisms has been identified as key to efficient intestinal anti-bacterial host defence and preservation of homeostasis. We hypothesized that glucocorticoid therapy may impair IL-22 expression, which should promote intestinal epithelial damage with the potential of subsequent bacterial translocation. High-dose corticosteroid therapy in Crohn's disease has been associated with an increased rate of abscess formation and ultimately with a higher risk of developing postoperative infectious complications, including abdominal sepsis. Thus, we sought to investigate effects of the prototypic glucocorticoid dexamethasone on IL-22 production in the context of bacterial infection. Enhanced IL-22 plasma levels were detectable in rat sepsis. Moreover, heat-inactivated Staphylococcus epidermidis, used as a prototypic activator of innate immunity, induced robust production of IL-22 by human peripheral blood mononuclear cells (PBMC). Here, we report for the first time that dexamethasone mediates remarkable suppression of IL-22 as detected in S. epidermidis-activated PBMC and rat sepsis, respectively. The data presented herein suggest that insufficient IL-22 function may contribute to impaired intestinal host defence in the context of corticosteroid therapy.
Ziesché
E
E
Pharmazentrum Frankfurt/ZAFES, Intensive Care Medicine and Pain Therapy, University Hospital Goethe University, 60590 Frankfurt am Main, Germany.
Scheiermann
P
P
Bachmann
M
M
Sadik
C D
CD
Hofstetter
C
C
Zwissler
B
B
Pfeilschifter
J
J
Mühl
H
H
D000818:Animals; D016022:Case-Control Studies; D002478:Cells, Cultured; D003864:Depression, Chemical; D003907:Dexamethasone / Q000031:analogs & derivatives / Q000627:therapeutic use*; D015870:Gene Expression / Q000187:drug effects; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D016209:Interleukin-8 / Q000235:genetics / Q000276:immunology; D007378:Interleukins / Q000235:genetics / Q000276:immunology*; D008297:Male; D023421:Models, Animal; D010538:Peritonitis / Q000188:drug therapy / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000276:immunology*; D013212:Staphylococcus epidermidis; D000097043:Interleukin-22
D003907:Dexamethasone; D005938:Glucocorticoids; D016753:Interleukin-10; D016209:Interleukin-8; D007378:Interleukins; D012333:RNA, Messenger; D000097043:Interleukin-22; C004180:dexamethasone 21-phosphate