Influence of standard treatment on ileal and colonic antimicrobial defensin expression in active Crohn's disease.
BACKGROUND
Crohn's Disease (CD), a chronic intestinal inflammation, is currently treated primarily by therapeutics which are directed against inflammatory responses. Recent findings though suggest a central role of the innate immune barrier in the pathophysiology. Important factors providing this barrier are antimicrobial peptides like the alpha- and beta-defensins. Little is known about in vivo effects of common drugs on their expression.


OBJECTIVE
To analyse the influence of corticosteroids, azathioprine and aminosalicylate treatment on ileal and colonic antimicrobial peptides in active CD and also assess the role of inflammation.


METHODS
We measured the expression of antimicrobial peptides and pro-inflammatory cytokines in 75 patients with active CD.


RESULTS
Ileal and colonic alpha- and beta-defensins as well as LL37 remained unaffected by corticosteroids, azathioprine or aminosalicylate treatment. Additionally, we did not observe a negative coherency between Paneth cell alpha-defensins and any measured cytokines. HBD2 and LL37 unlike HBD1 levels were linked to inflammatory cytokines and increased in highly inflamed samples.


CONCLUSIONS
Current oral drug treatment seems to have no major effect on the expression of antimicrobial peptides. In contrast to HBD2 and LL37, ileal levels of HD5 and HD6 and colonic HBD1 level are independent of current inflammation. Innovative drugs should aim to strengthen protective innate immunity.
Kübler
I
I
Robert-Bosch-Hospital, Stuttgart, Germany.
Koslowski
M J
MJ
Gersemann
M
M
Fellermann
K
K
Beisner
J
J
Becker
S
S
Rothfuss
K
K
Herrlinger
K R
KR
Stange
E F
EF
Wehkamp
J
J
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D001379:Azathioprine / Q000627:therapeutic use*; D003424:Crohn Disease / Q000188:drug therapy*; D023082:Defensins / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D055815:Young Adult
D000305:Adrenal Cortex Hormones; D000890:Anti-Infective Agents; D023082:Defensins; D007166:Immunosuppressive Agents; D001379:Azathioprine