Immunosuppressive effects via human intestinal dendritic cells of probiotic bacteria and steroids in the treatment of acute ulcerative colitis.
BACKGROUND
In ulcerative colitis (UC) gut bacteria drive inflammation. Bacterial recognition and T-cell responses are shaped by intestinal dendritic cells (DCs); therapeutic effects of probiotic bacteria may relate to modulation of intestinal DC. The probiotic mixture, VSL#3, increases interleukin (IL)-10 and downregulates IL-12p40 production by DC in vitro. We evaluated in vivo effects of oral VSL#3 and steroids on colonic DC in patients with acute UC.


METHODS
Rectal biopsies were obtained from patients with active UC before and after treatment with VSL#3, corticosteroids, or placebo, and from healthy controls. Myeloid colonic DC were studied from freshly isolated lamina propria cells using multicolor flow cytometry. Surface expression of activation markers, CD40, CD86, pattern recognition receptors, Toll-like receptor (TLR)-2 and TLR-4 were assessed. Changed function was measured from ongoing intracellular IL-10, IL-12p40, IL-6, and IL-13 production.


RESULTS
Acute UC colonic myeloid DC were producing more IL-10 and IL-12p40 than control DC (P = 0.01). In VSL#3-treated patients DC TLR-2 expression decreased (P < 0.05), IL-10 production increased and IL-12p40 production decreased (P < 0.005); 10/14 patients on VSL#3 showed a clinical response. Corticosteroids also resulted in increased IL-10 and reduced IL-12p40 production by DC. Conversely, in patients on placebo, TLR-2 expression and intensity of staining for IL-12p40 and IL-6 increased (all P < 0.05); 5/14 patients on placebo showed a clinical response (P = NS).


CONCLUSIONS
Despite small numbers of human colonic DC available, we showed that treatment of UC patients with probiotic VSL#3 and corticosteroids induced "favorable" intestinal DC function in vivo, increasing regulatory cytokines and lowering proinflammatory cytokines and TLR expression. These effects may contribute to therapeutic benefit.
Ng
Siew C
SC
Antigen Presentation Research Group, Faculty of Medicine, Imperial College London, Northwick Park and St Mark's Campus, Watford Road, Harrow, UK.
Plamondon
Sophie
S
Kamm
Michael A
MA
Hart
Ailsa L
AL
Al-Hassi
Hafid Omar
HO
Guenther
Thomas
T
Stagg
Andrew J
AJ
Knight
Stella C
SC
D000208:Acute Disease; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D001379:Azathioprine / Q000627:therapeutic use; D051940:B7-2 Antigen / Q000032:analysis / Q000276:immunology; D019013:CD40 Antigens / Q000032:analysis / Q000276:immunology; D003093:Colitis, Ulcerative / Q000188:drug therapy / Q000628:therapy*; D003106:Colon / Q000276:immunology* / Q000382:microbiology; D003713:Dendritic Cells / Q000276:immunology* / Q000382:microbiology; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D053762:Interleukin-12 Subunit p40 / Q000096:biosynthesis / Q000276:immunology; D018793:Interleukin-13 / Q000096:biosynthesis / Q000276:immunology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology; D008297:Male; D015122:Mercaptopurine / Q000627:therapeutic use; D019804:Mesalamine / Q000627:therapeutic use; D008875:Middle Aged; D019936:Probiotics / Q000627:therapeutic use*; D051192:Receptors, Pattern Recognition / Q000032:analysis / Q000276:immunology; D055815:Young Adult
D000305:Adrenal Cortex Hormones; D051940:B7-2 Antigen; D019013:CD40 Antigens; D007166:Immunosuppressive Agents; D053762:Interleukin-12 Subunit p40; D018793:Interleukin-13; D015850:Interleukin-6; D051192:Receptors, Pattern Recognition; D016753:Interleukin-10; D019804:Mesalamine; D015122:Mercaptopurine; D001379:Azathioprine